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İnam MG, İnam O, Gucer D, Park J, Amellal Y, Tezel TH, Tezel G. Obesity-related early structural alterations in the retina detected by optical coherence tomography. Diabetes Obes Metab 2025; 27:3262-3273. [PMID: 40116191 PMCID: PMC12046446 DOI: 10.1111/dom.16344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Revised: 03/05/2025] [Accepted: 03/05/2025] [Indexed: 03/23/2025]
Abstract
AIMS This retrospective cross-sectional study, using retinal spectral-domain optical coherence tomography (SD-OCT) scans, investigated obesity-related structural alterations in the retina. MATERIALS AND METHODS Ninety-two eyes of 92 healthy asymptomatic participants were categorized into two groups based on body mass index (BMI) measurements: non-obese (BMI < 25, 45%) and pre-obese/obese (BMI ≥ 25, 55%) to compare imaging parameters of different retinal layers. Structural parameters, including thickness and volume values, were obtained across distinct retinal layers segmented on SD-OCT scans. RESULTS The retinal nerve fibre layer volume was lower in the high-BMI group than in the low-BMI group (p = 0.048). However, the high-BMI group presented significantly higher inner nuclear layer volume than the low-BMI group (p = 0.036). In the region analysis, the retinal nerve fibre layer volume difference was prominent in the superior (p = 0.033) and inferior (p = 0.001) parafoveal and nasal perifoveal (p = 0.041) regions, while inner nuclear layer changes were prominent in the inferior (p = 0.009) perifoveal regions. A stepwise hierarchical binary logistic regression model, controlling for age and gender, pointed to significant associations of the regionally decreased retinal nerve fibre layer volume and increased inner nuclear layer volume with high BMI (p = 0.001). CONCLUSIONS Retinal SD-OCT imaging detected structural alterations in distinct retinal layers between healthy, asymptomatic individuals in non-obese and pre-obese/obese groups. Besides a decreased volume of the retinal nerve fibre layer, a significant increase was detected in the inner nuclear layer volume with a high BMI, possibly due to Müller glia responses to obesity-related osmotic, metabolic and inflammatory stress, awaiting further investigation.
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Affiliation(s)
- Maide Gözde İnam
- Department of Ophthalmology, Edward S. Harkness Eye Institute, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical CenterNew YorkNew YorkUSA
| | - Onur İnam
- Department of Ophthalmology, Edward S. Harkness Eye Institute, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical CenterNew YorkNew YorkUSA
- Department of Biophysics, Faculty of MedicineGazi UniversityAnkaraTurkey
| | - Doru Gucer
- Department of Ophthalmology, Edward S. Harkness Eye Institute, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical CenterNew YorkNew YorkUSA
| | - James Park
- Department of Ophthalmology, Edward S. Harkness Eye Institute, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical CenterNew YorkNew YorkUSA
| | | | - Tongalp H. Tezel
- Department of Ophthalmology, Edward S. Harkness Eye Institute, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical CenterNew YorkNew YorkUSA
| | - Gülgün Tezel
- Department of Ophthalmology, Edward S. Harkness Eye Institute, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical CenterNew YorkNew YorkUSA
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2
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Zhang N, Sun Q, Zhang J, Zhang R, Liu S, Zhao X, Ma J, Li X. Intrapancreatic adipocytes and beta cell dedifferentiation in human type 2 diabetes. Diabetologia 2025; 68:1242-1260. [PMID: 40072535 DOI: 10.1007/s00125-025-06392-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Accepted: 01/20/2025] [Indexed: 03/14/2025]
Abstract
AIMS/HYPOTHESIS Fat deposition in the pancreas is implicated in beta cell dysfunction and the progress of type 2 diabetes. However, there is limited evidence to confirm the correlation and explore how pancreatic fat links with beta cell dysfunction in human type 2 diabetes. This study aimed to examine the spatial relationship between pancreatic fat and islets in human pancreases. METHODS Histological analysis of pancreatic specimens from 50 organ donors (15 with type 2 diabetes, 35 without) assessed pancreatic fat content variation among individuals with diabetes and its correlation with estimated beta cell mass and cell distribution within islets. Bioinformatic analysis of single-cell RNA-seq of 11 type 2 diabetic donors (from the Human Pancreatic Analysis Project database) explored the impact of high pancreatic fat content on beta cell gene expression and cell fate. Validation of bioinformatic results was performed with the above diabetic pancreases. RESULTS Pancreatic fat content was higher in individuals with type 2 diabetes (10.24% [3.29-13.89%] vs 0.74% [0.34-5.11%], p<0.001), negatively correlated with estimated beta cell mass (r=-0.675, p=0.006) and positively with alpha-to-beta cell ratio (r=0.608, p=0.016). Enrichment analysis indicated that in diabetic donors with higher pancreatic fat content, the expression of ALDH1A3, beta cell dedifferentiation marker, in both alpha and beta cells was significantly increased, and in beta cells, the expression of NPY decreased. Pseudotime analysis revealed beta cell dedifferentiation and transdifferentiation towards alpha cells in diabetic donors with higher pancreatic fat content, with decreased expression of genes related to beta cell maturation and function, including INSM1, MafA and NPY. Concurrently, pathways related to inflammation and immune response were activated. Histologically, pancreatic fat content correlated positively with the percentage of beta cells positive for aldehyde dehydrogenase 1 family member A3 (ALDH1A3) within the islets (r=0.594, p=0.020) and the ALDH1A3 positivity rate in beta cells (r=0.615, p=0.015). And the number of T cells adjacent to adipocytes was related to the distribution pattern of adipocytes and the dedifferentiation phenotype in islets. CONCLUSIONS/INTERPRETATION Higher pancreatic fat content was accompanied by increased beta cell dedifferentiation in the individuals with diabetes. Clusters of adipocytes significantly contribute to higher pancreatic fat content and immune cell recruitment. Overall, the interactions among adipocytes, immune cells and beta cells in the pancreas microenvironment might contribute to beta cell failure and dedifferentiation in type 2 diabetes.
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Affiliation(s)
- Na Zhang
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Qiman Sun
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jiaxin Zhang
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ruonan Zhang
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Siyi Liu
- Fudan University, Shanghai, China
| | - Xuelian Zhao
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jing Ma
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xiaomu Li
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.
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3
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Cheng Y, Zhang K, Liu J, Liu G. Is orbital adipose tissue obesity-privileged? The relationship between small adipocyte size and metabolically healthy state from the view of orbital fat. J Endocrinol Invest 2025:10.1007/s40618-025-02568-7. [PMID: 40120074 DOI: 10.1007/s40618-025-02568-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Accepted: 03/09/2025] [Indexed: 03/25/2025]
Abstract
PURPOSE White adipose tissue (WAT) expands by increasing adipocyte size (hypertrophy) and/or number (hyperplasia) to handle excess energy and plays a key homeostatic role in lipid metabolism. Hypertrophic adipocytes have many impaired biological functions. In contrast, hyperplastic adipocytes can reduce the negative metabolic effects of obesity. Thus, understanding the mechanisms of adaptive WAT expansion is essential for optimizing lipid storage and preventing the adverse metabolic consequences of obesity. Hedgehog (Hh) signaling has been shown to improve adipose health and can be a pharmacological target to ameliorate obesity-induced metabolic abnormalities. Clinically, we found that the size of adipocytes in orbital fat (OF) is less affected by obesity, and we hypothesized that OF possesses a relatively metabolically healthy profile. METHODS To verify our hypothesis, we identified multiple hallmarks of healthy adipose tissue in OF using a combination of bioinformatics-based transcriptomics analyses and experimental methods. RESULTS Our results revealed that compared with abdominal subcutaneous fat (SF), OF had a smaller cell size, more dynamic ability to remodel the adipose extracellular matrix (ECM), higher vascular supply, and less macrophage infiltration. OF also showed promising adipogenic and proliferative capabilities and a healthy adipocytokine secretion pattern. Moreover, the Hh signaling was activated in OF and may influence depot-specific adipose health. CONCLUSION These findings collectively support that OF is generally in a naturally metabolically healthy state with high expandability and obesity-free privilege, providing new therapeutic ideas for obesity-related metabolic dysfunctions.
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Affiliation(s)
- Y Cheng
- Department of Plastic and Reconstructive Surgery, School of Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China
| | - K Zhang
- Department of Plastic and Reconstructive Surgery, School of Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China
| | - J Liu
- Department of Burn and Plastic Surgery, The Third People's Hospital of Bengbu, Bengbu, Anhui, China.
| | - G Liu
- Department of Plastic and Reconstructive Surgery, School of Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
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Wang Y, Zhang X, Li X, Cheng M, Cui X. The vascular microenvironment and its stem cells regulate vascular homeostasis. Front Cell Dev Biol 2025; 13:1544129. [PMID: 40114970 PMCID: PMC11922910 DOI: 10.3389/fcell.2025.1544129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Accepted: 02/17/2025] [Indexed: 03/22/2025] Open
Abstract
The vascular microenvironment comprises of anatomical structures, extracellular matrix components, and various cell populations, which play a crucial role in regulating vascular homeostasis and influencing vascular structure and function. Under physiological conditions, intrinsic regulation of the vascular microenvironment is required to sustain vascular homeostasis. In contrast, under pathological conditions, alterations to this microenvironment lead to vascular injury and pathological remodeling. According to the anatomy, the vascular microenvironment can be subdivided into three sections from the inside out. The vascular endothelial microenvironment, centered on vascular endothelial cells (VECs), includes the extracellular matrix and various vascular physicochemical factors. The VECs interact with vascular physicochemical factors to regulate the function of various parenchymal cells, including hepatocytes, neurons and tumor cells. The vascular wall microenvironment, comprising the vasa vasorum and their unique stem/progenitor cell niches, plays a pivotal role in vascular inflammation and pathological remodeling. Additionally, the perivascular microenvironment, which includes perivascular adipose tissue, consists of adipocytes and stem cells, which contribute to the pathological processes of atherosclerosis. It is anticipated that targeted regulation of the vascular microenvironment will emerge as a novel approach for the treatment of various diseases. Accordingly, this review will examine the structure of the vascular microenvironment, the regulation of vascular function by vascular cells and stem/progenitor cells, and the role of the vascular microenvironment in regulating cardiovascular diseases.
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Affiliation(s)
- Yanhui Wang
- Medical Physiology Laboratory, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, China
| | - Xiaoyun Zhang
- Medical Physiology Laboratory, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, China
| | - Xin Li
- Medical Physiology Laboratory, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, China
| | - Min Cheng
- Medical Physiology Laboratory, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, China
| | - Xiaodong Cui
- Medical Physiology Laboratory, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, China
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5
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Yi M, Wang X, Li Y, Li X, Si J, Zhang Y, Xiao K, Sun L, Zhang H, Sun J, Liu Z, Lin J, Xie Y, Zhang B, Zhao J, Chu X, Li J. Association between Metabolic Syndrome Score and Subclinical Atherosclerosis. Rev Cardiovasc Med 2025; 26:26811. [PMID: 40160566 PMCID: PMC11951480 DOI: 10.31083/rcm26811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Revised: 12/12/2024] [Accepted: 01/13/2025] [Indexed: 04/02/2025] Open
Abstract
Background Previous studies have presented conflicting results on the correlation between metabolic syndrome (MetS) and subclinical atherosclerosis. However, the binary MetS definition cannot reflect the severity of metabolic disorders continuously and dynamically. The present study calculated the MetS score and explored the association between MetS score and subclinical atherosclerosis. Methods A total of 840 participants were included in this observational, cross-sectional study; 66.55% of participants were men, and the median age was 61.00 years (53.00, 67.00). Brachial-ankle pulse wave velocity (baPWV) and brachial flow-mediated dilation (bFMD) values were measured from October 2016 to January 2020. Spearman's correlation and multiple linear regression analyses were conducted to explore the correlation between the MetS score and baPWV and bFMD. Arterial stiffness was defined as baPWV ≥1400 cm/s, while endothelial dysfunction was described as bFMD >6%. Multiple logistic regression was performed to explore the effects of MetS and MetS score on arterial stiffness and endothelial dysfunction. Results The MetS score was significantly associated with baPWV (β = 73.59, 95% CI (42.70, 104.48); p < 0.001) and bFMD (β = -0.43, 95% CI (-0.75, -0.10); p = 0.010) after adjusting for covariates. Compared with the binary definition of MetS, the MetS score was a more significant predictor for arterial stiffness (odds ratio, OR = 2.63, 95% CI (1.85, 3.74); p < 0.001) and endothelial dysfunction (OR = 1.33, 95% CI (1.01, 1.76); p = 0.040). Leukocyte count (r = 0.32; p < 0.001) and high-sensitivity C-reactive protein (hs-CRP) (r = 0.17; p < 0.001) values were related to the MetS score. Conclusions The MetS score is a clinically accessible assessment of metabolic status that can identify individuals at higher risk of subclinical atherosclerosis.
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Affiliation(s)
- Ming Yi
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 100053 Beijing, China
| | - Xinyi Wang
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 100053 Beijing, China
| | - Yan Li
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 100053 Beijing, China
| | - Xuewen Li
- Department of the General Medicine, Characteristic Medical Center of Chinese People’s Armed Police Force, 300162 Tianjin, China
| | - Jin Si
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 100053 Beijing, China
| | - Yinghua Zhang
- Department of Cardiology, Chui Yang Liu Hospital Affiliated to Tsinghua University, 100021 Beijing, China
| | - Keling Xiao
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 100053 Beijing, China
| | - Lijie Sun
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 100053 Beijing, China
| | - Haoyu Zhang
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 100053 Beijing, China
| | - Jinghao Sun
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 100053 Beijing, China
| | - Zhaoli Liu
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 100053 Beijing, China
| | - Jiaying Lin
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 100053 Beijing, China
| | - Yuxin Xie
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 100053 Beijing, China
| | - Bingyan Zhang
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 100053 Beijing, China
| | - Jing Zhao
- Health Management Center, Xuanwu Hospital, Capital Medical University, 100053 Beijing, China
| | - Xi Chu
- Health Management Center, Xuanwu Hospital, Capital Medical University, 100053 Beijing, China
| | - Jing Li
- Department of Geriatrics, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, 100053 Beijing, China
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6
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Desmond LW, Dawud LM, Kessler LR, Akonom T, Hunter EAH, Holbrook EM, Andersen ND, Sterrett JD, Boateng DA, Stuart BJ, Guerrero L, Gebert MJ, Tsai PS, Langgartner D, Reber SO, Frank MG, Lowry CA. Protective effects of Mycobacterium vaccae ATCC 15483 against "Western"-style diet-induced weight gain and visceral adiposity in adolescent male mice. Brain Behav Immun 2025; 125:249-267. [PMID: 39709061 DOI: 10.1016/j.bbi.2024.12.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2024] [Revised: 11/21/2024] [Accepted: 12/16/2024] [Indexed: 12/23/2024] Open
Abstract
The prevalence of noncommunicable inflammatory disease is increasing in modern urban societies, posing significant challenges to public health. Novel prevention and therapeutic strategies are needed to effectively deal with this issue. One promising approach is leveraging microorganisms such as Mycobacterium vaccae ATCC 15483, known for its anti-inflammatory, immunoregulatory, and stress-resilience properties. This study aimed to assess whether weekly subcutaneous administrations of a whole-cell, heat-killed preparation of M. vaccae ATCC 15483 (eleven injections initiated one week before the onset of the diet intervention), relative to vehicle injections, in adolescent male C57BL/6N mice can mitigate inflammation associated with Western-style diet-induced obesity, which is considered a risk factor for a number of metabolic and inflammatory diseases. Our results show that treatment with M. vaccae ATCC 15483 prevented Western-style diet-induced excessive weight gain, visceral adipose tissue accumulation, and elevated plasma leptin concentrations. The Western-style diet, relative to a control diet condition, decreased alpha diversity and altered the community composition of the gut microbiome, increasing the Bacillota to Bacteroidota ratio (formerly referred to as the Firmicutes to Bacteroidetes ratio). Despite the finding that M. vaccae ATCC 15483 prevented Western-style diet-induced excessive weight gain, visceral adipose tissue accumulation, and elevated plasma leptin concentrations, it had no effect on the diversity or community composition of the gut microbiome, suggesting that it acts downstream of the gut microbiome to alter immunometabolic signaling. M. vaccae ATCC 15483 reduced baseline levels of biomarkers of hippocampal neuroinflammation and microglial priming, such as Nfkbia and Nlrp3, and notably decreased anxiety-like defensive behavioral responses. The current findings provide compelling evidence supporting the potential for M. vaccae ATCC 15483 as a promising intervention for prevention or treatment of adverse immunometabolic outcomes linked to the consumption of a Western-style diet and the associated dysbiosis of the gut microbiome.
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Affiliation(s)
- Luke W Desmond
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
| | - Lamya'a M Dawud
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
| | - Lyanna R Kessler
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
| | - Tyler Akonom
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
| | - Elizabeth A H Hunter
- Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA; Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, CO 80309, USA.
| | - Evan M Holbrook
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
| | - Nathan D Andersen
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
| | - John D Sterrett
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
| | - Dennis A Boateng
- Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, CO 80309, USA.
| | - Barbara J Stuart
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
| | - Lucas Guerrero
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
| | - Matthew J Gebert
- Department of Ecology and Evolutionary Biology, Cooperative Institute for Research in Environmental Sciences (CIRES), University of Colorado Boulder, Boulder, CO 80309, USA; Center for Microbial Exploration, University of Colorado Boulder, Boulder, CO 80309, USA.
| | - Pei-San Tsai
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
| | - Dominik Langgartner
- Laboratory for Molecular Psychosomatics, Department of Psychosomatic Medicine and Psychotherapy, Ulm University Medical Center, D-89081, Ulm, Germany.
| | - Stefan O Reber
- Laboratory for Molecular Psychosomatics, Department of Psychosomatic Medicine and Psychotherapy, Ulm University Medical Center, D-89081, Ulm, Germany.
| | - Matthew G Frank
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
| | - Christopher A Lowry
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA; Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA; Center for Microbial Exploration, University of Colorado Boulder, Boulder, CO 80309, USA; Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA; Department of Physical Medicine and Rehabilitation and Center for Neuroscience, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
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7
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Echols JT, Wang S, Patel AR, Hogwood AC, Abbate A, Epstein FH. Fatty acid composition MRI of epicardial adipose tissue: Methods and detection of proinflammatory biomarkers in ST-segment elevation myocardial infarction patients. Magn Reson Med 2025; 93:519-535. [PMID: 39323040 PMCID: PMC11604849 DOI: 10.1002/mrm.30285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 07/27/2024] [Accepted: 08/20/2024] [Indexed: 09/27/2024]
Abstract
PURPOSE To develop a method for quantifying the fatty acid composition (FAC) of human epicardial adipose tissue (EAT) using accelerated MRI and identify its potential for detecting proinflammatory biomarkers in patients with ST-segment elevation myocardial infarction (STEMI). METHODS A multi-echo radial gradient-echo sequence was developed for accelerated imaging during a breath hold using a locally low-rank denoising technique to reconstruct undersampled images. FAC mapping was achieved by fitting the multi-echo images to a multi-resonance complex signal model based on triglyceride characterization. Validation of the method was assessed using a phantom comprised of multiple oils. In vivo imaging was performed in STEMI patients (n = 21; 14 males/seven females). FAC was quantified in EAT, subcutaneous AT, and abdominal visceral AT. RESULTS Phantom validation demonstrated strong correlations (r > 0.97) and statistical significance (p < 0.0001) between measured and reference proton density fat fraction and FAC values. In vivo imaging of STEMI patients revealed a distinct EAT FAC profile compared to subcutaneous AT and abdominal visceral AT. EAT FAC parameters had significant correlations with left ventricular (LV) end-diastolic volume index (p < 0.05), LV end-systolic volume index (p < 0.05), and LV mass index (p < 0.05). CONCLUSIONS Accelerated MRI enabled accurate quantification of human EAT FAC. The relationships between the EAT FAC profile and LV structure and function in STEMI patients suggest the potential of EAT FAC MRI as a biomarker for adipose tissue quality and inflammatory status in cardiovascular disease.
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Affiliation(s)
- John T. Echols
- Biomedical EngineeringUniversity of VirginiaCharlottesvilleVirginiaUSA
| | - Shuo Wang
- Division of Cardiovascular MedicineUniversity of VirginiaCharlottesvilleVirginiaUSA
| | - Amit R. Patel
- Division of Cardiovascular MedicineUniversity of VirginiaCharlottesvilleVirginiaUSA
| | - Austin C. Hogwood
- Robert M. Berne Cardiovascular Research CenterUniversity of VirginiaCharlottesvilleVirginiaUSA
| | - Antonio Abbate
- Division of Cardiovascular MedicineUniversity of VirginiaCharlottesvilleVirginiaUSA
- Robert M. Berne Cardiovascular Research CenterUniversity of VirginiaCharlottesvilleVirginiaUSA
| | - Frederick H. Epstein
- Biomedical EngineeringUniversity of VirginiaCharlottesvilleVirginiaUSA
- Robert M. Berne Cardiovascular Research CenterUniversity of VirginiaCharlottesvilleVirginiaUSA
- RadiologyUniversity of VirginiaCharlottesvilleVirginiaUSA
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8
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Di Porzio A, Barrella V, Cigliano L, Mauriello G, Troise AD, Scaloni A, Iossa S, Mazzoli A. Diet-induced impairment of skeletal muscle and adipose tissue metabolic homeostasis and its prevention by probiotic administration. Pflugers Arch 2025; 477:223-239. [PMID: 39537965 DOI: 10.1007/s00424-024-03041-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 09/27/2024] [Accepted: 10/30/2024] [Indexed: 11/16/2024]
Abstract
Western dietary pattern is one of the main contributors to the increased risk of obesity and chronic diseases, through oxidative stress and inflammation, that are the two key mechanisms targeting metabolic organs, such as skeletal muscle and adipose tissue. The chronic exposure to high levels of dietary fatty acids can increase the amount of intramyocellular lipids in skeletal muscle, altering glucose homeostasis and contributing to a reduction in mitochondrial oxidative capacity. Probiotic administration is a promising approach as preventive strategy to attenuate metabolic damage induced by Western diet. Here, we investigated the beneficial effect of Limosillactobacillus reuteri DSM 17938 on the inflammatory state and oxidative balance in the skeletal muscle and adipose tissue of adult rats fed a western diet for 8 weeks, focusing on the role of skeletal muscle mitochondria. Limosillactobacillus reuteri DSM 17938 administration protected the skeletal muscle from mitochondrial dysfunction and oxidative stress, preventing the establishment of inflammation and insulin resistance. Interestingly, a further beneficial effect of the probiotic was exerted on body composition, favoring the deposition of protein mass and preventing adipose tissue hypertrophy and inflammation. These results open the possibility for the use of this probiotic in therapeutic approaches for nutrition-related diseases.
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Affiliation(s)
- Angela Di Porzio
- Department of Biology, University of Naples Federico II, 80126, Naples, Italy
| | - Valentina Barrella
- Department of Biology, University of Naples Federico II, 80126, Naples, Italy
- National Biodiversity Future Center, 90133, Palermo, Italy
| | - Luisa Cigliano
- Department of Biology, University of Naples Federico II, 80126, Naples, Italy
- Task Force on Microbiome Studies, University of Naples Federico II, Naples, Italy
| | - Gianluigi Mauriello
- Department of Agricultural Sciences, University of Naples Federico II, 80055, Portici, Italy
| | - Antonio Dario Troise
- Proteomics, Metabolomics and Mass Spectrometry Laboratory, Institute for the Animal Production System in the Mediterranean Environment, National Research Council, 80055, Portici, Italy
| | - Andrea Scaloni
- Proteomics, Metabolomics and Mass Spectrometry Laboratory, Institute for the Animal Production System in the Mediterranean Environment, National Research Council, 80055, Portici, Italy
| | - Susanna Iossa
- Department of Biology, University of Naples Federico II, 80126, Naples, Italy.
- National Biodiversity Future Center, 90133, Palermo, Italy.
- Task Force on Microbiome Studies, University of Naples Federico II, Naples, Italy.
| | - Arianna Mazzoli
- Department of Biology, University of Naples Federico II, 80126, Naples, Italy.
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9
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Zhong L, Jiang W, Liu Y, Huang J. Association between obesity and Bell's palsy by combining Mendelian randomization and network pharmacology. Medicine (Baltimore) 2025; 104:e41111. [PMID: 39889190 PMCID: PMC11789879 DOI: 10.1097/md.0000000000041111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 11/13/2024] [Accepted: 12/10/2024] [Indexed: 02/02/2025] Open
Abstract
BACKGROUND The issue of obesity has emerged as a significant global health challenge; nevertheless, the association between Bell's palsy (BP) and obesity remains ambiguous. In this study, the Mendelian randomization (MR) approach was employed to investigate their relationship, while network pharmacology methods were utilized to unveil the underlying mechanisms. METHODS We utilized single nucleotide polymorphisms closely linked to obesity and BP as instrumental variables for the MR analysis. Four robust bidirectional MR analysis methods, namely inverse variance weighting (IVW), weighted median, weighted mode, and MR-Egger were employed to assess the association between obesity and BP. Additionally, sensitivity analysis was conducted to evaluate levels of heterogeneity, sensitivity, and stability. Furthermore, we identified therapeutic targets associated with obesity and BP. Subsequently, a protein-protein interaction network analysis was conducted. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were employed to investigate potential mechanisms underlying the relationship between obesity and BP. RESULTS The IVW analysis demonstrated a significant positive correlation between obesity and BP (odds ratio [OR] = 1.267, 95% confidence interval [95% CI] = 1.049-1.530, P = .013). However, there was no evidence to suggest that BP increased the risk of obesity. Furthermore, network pharmacology analysis revealed that the 2 diseases shared a total of 712 common targets. GO enrichment analysis shows that this process mainly regulates chemical synaptic signal transmission by modulating receptor signaling factor activity, receptor ligand activity, etc. KEGG enrichment analysis shows that the EGFR/PI3K/Akt signaling pathway plays a significant role in this process. CONCLUSION Our study findings suggest that obesity may increase the risk of BP, and its underlying mechanism may potentially involve regulating chemical synaptic transmission through the EFGR/PI3K/Akt signaling pathway.
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Affiliation(s)
- Li Zhong
- Gerontology Medicine Department, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, Sichuan, China
| | - Wei Jiang
- Rehabilitation Medicine Department, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, Sichuan, China
| | - Yan Liu
- Gerontology Medicine Department, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, Sichuan, China
| | - Juan Huang
- Rehabilitation Medicine Department, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, Sichuan, China
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10
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Abe K, Sasano T, Soejima Y, Fukayama H, Maeda S, Furukawa T. Hypermethylation of Hif3a and Ifltd1 is associated with atrial remodeling in pressure-overload murine model. Sci Rep 2025; 15:2699. [PMID: 39837857 PMCID: PMC11751168 DOI: 10.1038/s41598-025-85382-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2024] [Accepted: 01/02/2025] [Indexed: 01/23/2025] Open
Abstract
Atrial remodeling is a major pathophysiological mechanism of atrial fibrillation (AF). Atrial remodeling progresses with aging and background diseases, including hypertension, heart failure, and AF itself. However, its mechanism of action and reversibility have not been completely elucidated. In this study, we investigated the involvement of DNA methylation in atrial remodeling. Mice underwent transverse aortic constriction (TAC) to generate a pressure overload model. After 14 days, the TAC-operated mice showed a significant increase in the atrium/body weight ratio and deposition of collagen fibers in the atria. A comprehensive analysis using RNA-sequencing (RNA-Seq) and methyl-CpG-binding domain sequencing (MBD-Seq) in the left atrial tissue identified Hif3a and Ifltd1 as showing increased DNA methylation in their promoter regions and decreased RNA expression. In addition, we created a transient pressure overload model by removing the aortic constriction 3 or 7 days after the initial TAC procedure (R3 or R7 groups). A reduction in RNA expression was achieved at R3 for Hif3a and at R7 for Ifltd1. Heterozygous Dnmt1 gene-targeting mice (Dnmt1mut) showed disappearance of the reduction in RNA expression and an increase in the atrium/body weight ratio. Altogether, DNA methylation contributed to at least part of atrial remodeling in the pressure overload mouse model.
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Affiliation(s)
- Keiko Abe
- Department of Dental Anesthesiology and Orofacial Pain Management, Institute of Science Tokyo, Tokyo, Japan
- Department of Cardiovascular Medicine, Institute of Science Tokyo, 1-5-45, Yushima, Bunkyo-ku, Tokyo, Japan
| | - Tetsuo Sasano
- Department of Cardiovascular Medicine, Institute of Science Tokyo, 1-5-45, Yushima, Bunkyo-ku, Tokyo, Japan.
| | - Yurie Soejima
- Department of Pathology and Anatomical Sciences, Institute of Science Tokyo, Tokyo, Japan
| | - Haruhisa Fukayama
- Department of Dental Anesthesiology and Orofacial Pain Management, Institute of Science Tokyo, Tokyo, Japan
| | - Shigeru Maeda
- Department of Dental Anesthesiology and Orofacial Pain Management, Institute of Science Tokyo, Tokyo, Japan
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Krueger ABC, Zhu X, Siddiqi S, Whitehead EC, Tang H, Jordan KL, Lerman A, Lerman LO. Mesenchymal Stem/Stromal Cells Reverse Adipose Tissue Inflammation in Pigs with Metabolic Syndrome and Renovascular Hypertension. Cells 2025; 14:40. [PMID: 39791741 PMCID: PMC11720192 DOI: 10.3390/cells14010040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Revised: 12/28/2024] [Accepted: 12/29/2024] [Indexed: 01/12/2025] Open
Abstract
Metabolic syndrome (MetS) is associated with low-grade inflammation, which can be exacerbated by renal artery stenosis (RAS) and renovascular hypertension, potentially worsening outcomes through pro-inflammatory cytokines. This study investigated whether mesenchymal stem/stromal cells (MSCs) could reduce fat inflammation in pigs with MetS and RAS. Twenty-four pigs were divided into Lean (control), MetS, MetS + RAS, and MetS + RAS + MSCs. In the MSC-treated group, autologous adipose-derived MSCs (107 cells) were injected into the renal artery six weeks after RAS induction. After four weeks, fat volumes and inflammatory markers were assessed. MSC treatment reduced levels of pro-inflammatory cytokines (MCP-1, TNF-a, IL-6) in the renal vein blood and in perirenal fat. The MSCs also decreased fat fibrosis, restored adipocyte size, and altered adipogenesis-related gene expression, particularly in the perirenal fat. These effects were less pronounced in subcutaneous fat. The MSC therapy attenuated fat inflammation and improved metabolic outcomes in pigs with MetS + RAS, suggesting that adipose-derived MSCs may offer a promising therapeutic approach for metabolic disorders.
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Affiliation(s)
- Alexander B. C. Krueger
- Division of Nephrology & Hypertension, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA; (A.B.C.K.); (X.Z.); (E.C.W.); (H.T.); (K.L.J.)
| | - Xiangyang Zhu
- Division of Nephrology & Hypertension, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA; (A.B.C.K.); (X.Z.); (E.C.W.); (H.T.); (K.L.J.)
| | - Sarosh Siddiqi
- Division of Nephrology & Hypertension, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA; (A.B.C.K.); (X.Z.); (E.C.W.); (H.T.); (K.L.J.)
| | - Emma C. Whitehead
- Division of Nephrology & Hypertension, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA; (A.B.C.K.); (X.Z.); (E.C.W.); (H.T.); (K.L.J.)
| | - Hui Tang
- Division of Nephrology & Hypertension, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA; (A.B.C.K.); (X.Z.); (E.C.W.); (H.T.); (K.L.J.)
| | - Kyra L. Jordan
- Division of Nephrology & Hypertension, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA; (A.B.C.K.); (X.Z.); (E.C.W.); (H.T.); (K.L.J.)
| | - Amir Lerman
- Department of Cardiovascular Diseases, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA;
| | - Lilach O. Lerman
- Division of Nephrology & Hypertension, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA; (A.B.C.K.); (X.Z.); (E.C.W.); (H.T.); (K.L.J.)
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12
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Fikre D, Hawulte Ayele B, Sime A, Tebeje F, Weldegebreal F. Prevalence of work-related musculoskeletal disorder and ergonomic risk practice among medical laboratory professionals at health facilities of eastern Ethiopia. Front Public Health 2024; 12:1443217. [PMID: 39749243 PMCID: PMC11694512 DOI: 10.3389/fpubh.2024.1443217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Accepted: 10/30/2024] [Indexed: 01/04/2025] Open
Abstract
Background Musculoskeletal disorders represent a significant occupational problem due to poor ergonomic workstations among medical laboratory professionals; however, there is limited information regarding ergonomic-related musculoskeletal disorders among laboratory personnel in Ethiopia, particularly in eastern Ethiopia. Methods An institutional-based cross-sectional study design was implemented among 241 Medical Laboratory Professionals (MLPs) from December 20, 2023, to January 20, 2024. A standardized questionnaire adapted from the Nordic musculoskeletal questionnaire and a combination of self-administered surveys and direct observational techniques was used for data collection. Bivariate and multivariable logistic regression analyses were used to determine factors associated with musculoskeletal disorders with findings presented through Odds ratios and a 95% Confidence Interval (CI), and statistical significance was declared at p-value <0.05. Result This study showed that over the past 12 months, 142 (58.9%; 95% CI: 52.0, 65.0) Medical Laboratory professionals reported work-related musculoskeletal disorders at least in one of the nine body parts. Age 36 and above years (AOR = 1.51; 95% CI: 1.02, 6.01), being female (AOR = 1.89; 95% CI: 1.09, 5.04), work experience 10-15 years (AOR = 3.99; 95% CI: 1.6, 9.4), work experience >15 years (AOR = 4.13; 95% CI: 1.52, 10.81), sitting time 4 and above hours (AOR = 2.25; 95% CI: 1.10, 4.63), patient load >300 (AOR = 2.67; 95% CI: 1.12, 7.46), and being overweight (AOR = 1.67; 95% CI: 1.04, 6.03) were factors significantly associated. Conclusion The prevalence of work-related musculoskeletal disorders was found to be higher among Medical Laboratory Professionals as compared to previous research conducted in Ethiopia. It is recommended to regularly evaluate workstations to reduce strain through adjustments in the chair and bench heights and implement task rotation to reduce repetitive movements and distribute physical demands among staff, in addition to that, adjust work schedules to include intermittent breaks. Tailored ergonomic solutions and flexible arrangements should be provided for female professionals who are at a higher risk for work-related musculoskeletal disorders. Furthermore, conducting routine health screenings to detect early signs of musculoskeletal disorders for timely intervention, as well as enhancing awareness among Medical Laboratory Professionals, are essential measures to mitigate ergonomic risk practice.
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Affiliation(s)
- Dagim Fikre
- Bisidimo General Hospital Health Science College, Bisidimo, Ethiopia
| | - Behailu Hawulte Ayele
- School of Public Health, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia
| | - Akewok Sime
- School of Medical Laboratory Sciences, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia
| | - Fikru Tebeje
- School of Medical Laboratory Sciences, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia
| | - Fitsum Weldegebreal
- School of Medical Laboratory Sciences, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia
- Laboratory Bacteriology Research, Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
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Nagagata BA, Mandarim-de-Lacerda CA, Aguila MB. Melatonin-Supplemented Obese Female Mice Show Less Inflammation in Ovarian Adipocytes and Browning in Subcutaneous Adipocytes. Cell Biochem Funct 2024; 42:e70034. [PMID: 39707618 DOI: 10.1002/cbf.70034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 10/24/2024] [Accepted: 12/10/2024] [Indexed: 12/23/2024]
Abstract
We hypothesized that melatonin (Mel) supplementation may offer therapeutic benefits for obesity, particularly in women. Therefore, the study evaluated Mel's effects on white adipose tissue (WAT) in diet-induced obese female mice. Four-week-old C57BL/6 females were assigned to either a control diet (C group) or a high-fat diet (HF group) for 6 weeks (n = 20/group). Following this, Mel was administered (10 mg/kg/day) for 8 weeks (n = 10/group), resulting in four groups: C, CMel, HF, and HFMel. The HF group developed obesity. HFMel displayed reduced fat pad size, lower plasma insulin, and improved glucose tolerance and insulin resistance compared to HF. In ovarian WAT (oWAT), HFMel versus HF showed reduced pro-inflammatory markers, less endoplasmic reticulum (ER) stress, and smaller adipocyte size. In subcutaneous WAT (sWAT), HFMel versus HF demonstrated increased adipocyte multiloculation, higher uncoupling protein-1 expression, and elevated thermogenic gene expression. Principal component analysis of gene expressions in oWAT and sWAT revealed significant differences: in oWAT, ER stress and inflammation markers were linked to the HF group, while HFMel and CMel clustered together, indicating a beneficial Mel effect. In sWAT, HFMel and CMel clustered on the opposite side of HF, which is associated with thermogenic gene expressions. In conclusion, the findings demonstrate that Mel supplementation in obese female mice, even when maintained on an HF diet, effectively modulated weight gain and reduced ovarian and subcutaneous fat accumulation. Mel supplementation positively influenced insulin resistance, inflammation, and ER stress while promoting thermogenesis in WAT in obese female mice.
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Affiliation(s)
- Brenda A Nagagata
- Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Center, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Carlos A Mandarim-de-Lacerda
- Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Center, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Marcia Barbosa Aguila
- Laboratory of Morphometry, Metabolism and Cardiovascular Disease, Biomedical Center, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil
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14
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Wu RL, Chen N, Chen Y, Wu X, Ko CY, Chen XY. Visceral Adiposity as an Independent Risk Factor for Diabetic Peripheral Neuropathy in Type 2 Diabetes Mellitus: A Retrospective Study. J Diabetes Res 2024; 2024:9912907. [PMID: 39559714 PMCID: PMC11573447 DOI: 10.1155/2024/9912907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Accepted: 10/14/2024] [Indexed: 11/20/2024] Open
Abstract
Background: Diabetic peripheral neuropathy (DPN) impacts approximately 50% of individuals with Type 2 diabetes mellitus (T2DM), leading to severe complications such as foot ulcers and amputations. Notably, visceral adiposity is increasingly recognized as a pivotal factor in augmenting the risk of DPN. We aim to evaluate the correlation between obesity-related body composition, particularly visceral fat, and DPN to facilitate early identification of high-risk patients with T2DM. Methods: This cross-sectional analysis encompassed 113 T2DM patients from the Department of Endocrinology and Metabolism at the Second Affiliated Hospital of Fujian Medical University, conducted between September 2020 and January 2021. Patients were categorized into two cohorts: those with DPN (DPN group) and those without (NDPN group). We utilized bioelectrical impedance analysis (BIA) to determine body measurements, such as weight and visceral fat area, in addition to collecting clinical and biochemical data. Logistic regression was employed to analyze the data. Results: The study uncovered a statistically significant difference in the visceral fat area between the DPN and NDPN groups (p = 0.048). Through multivariate logistic regression analysis, the visceral fat area was identified as an independent risk factor for DPN among T2DM patients (OR 1.027; 95% CI 1.004-1.051, p = 0.022). Other significant risk factors included the duration of diabetes and the presence of diabetic retinopathy. Conclusion: The visceral fat area serves as an independent risk factor for DPN in individuals with T2DM. Implementing measures to assess and manage visceral obesity could be vital in the prevention and management of DPN. This underscores the value of technologies such as BIA in clinical and community settings for early intervention.
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Affiliation(s)
- Rui-Ling Wu
- Department of Clinical Nutrition, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Niyao Chen
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Yanni Chen
- Department of Endocrinology, Shishi General Hospital, Quanzhou, China
| | - Xiaohong Wu
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Chih-Yuan Ko
- Department of Clinical Nutrition, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
| | - Xiao-Yu Chen
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
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15
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Myers JW, Park WY, Eddie AM, Shinde AB, Prasad P, Murphy AC, Leonard MZ, Pinette JA, Rampy JJ, Montufar C, Shaikh Z, Hickman TT, Reynolds GN, Winn NC, Lantier L, Peck SH, Coate KC, Stein RW, Carrasco N, Calipari ES, McReynolds MR, Zaganjor E. Systemic inhibition of de novo purine biosynthesis prevents weight gain and improves metabolic health by increasing thermogenesis and decreasing food intake. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.10.28.620705. [PMID: 39553975 PMCID: PMC11566042 DOI: 10.1101/2024.10.28.620705] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/19/2024]
Abstract
Objective Obesity is a major health concern, largely because it contributes to type 2 diabetes mellitus (T2DM), cardiovascular disease, and various malignancies. Increase in circulating amino acids and lipids, in part due to adipose dysfunction, have been shown to drive obesity-mediated diseases. Similarly, elevated purines and uric acid, a degradation product of purine metabolism, are found in the bloodstream and in adipose tissue. These metabolic changes are correlated with metabolic syndrome, but little is known about the physiological effects of targeting purine biosynthesis. Methods To determine the effects of purine biosynthesis on organismal health we treated mice with mizoribine, an inhibitor of inosine monophosphate dehydrogenase 1 and 2 (IMPDH1/2), key enzymes in this pathway. Mice were fed either a low-fat (LFD; 13.5% kcal from fat) or a high-fat (HFD; 60% kcal from fat) diet for 30 days during drug or vehicle treatment. We ascertained the effects of mizoribine on weight gain, body composition, food intake and absorption, energy expenditure, and overall metabolic health. Results Mizoribine treatment prevented mice on a HFD from gaining weight, but had no effect on mice on a LFD. Body composition analysis demonstrated that mizoribine significantly reduced fat mass but did not affect lean mass. Although mizoribine had no effect on lipid absorption, food intake was reduced. Furthermore, mizoribine treatment induced adaptive thermogenesis in skeletal muscle by upregulating sarcolipin, a regulator of muscle thermogenesis. While mizoribine-treated mice exhibited less adipose tissue than controls, we did not observe lipotoxicity. Rather, mizoribine-treated mice displayed improved glucose tolerance and reduced ectopic lipid accumulation. Conclusions Inhibiting purine biosynthesis prevents mice on a HFD from gaining weight, and improves their metabolic health, to a significant degree. We also demonstrated that the purine biosynthesis pathway plays a previously unknown role in skeletal muscle thermogenesis. A deeper mechanistic understanding of how purine biosynthesis promotes thermogenesis and decreases food intake may pave the way to new anti-obesity therapies. Crucially, given that many purine inhibitors have been FDA-approved for use in treating various conditions, our results indicate that they may benefit overweight or obese patients.
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Affiliation(s)
- Jacob W. Myers
- Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Woo Yong Park
- Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Alexander M. Eddie
- Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Abhijit B. Shinde
- Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Praveena Prasad
- Department of Biochemistry and Molecular Biology, Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA
| | - Alexandria C. Murphy
- Department of Biochemistry and Molecular Biology, Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA
| | - Michael Z. Leonard
- Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA
- Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN, USA
| | - Julia A. Pinette
- Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Jessica J. Rampy
- Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA
- Department of Cellular & Molecular Physiology, Yale University, New Haven, CT, USA
| | - Claudia Montufar
- Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Zayedali Shaikh
- Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Tara T. Hickman
- Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Garrett N. Reynolds
- Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Nathan C. Winn
- Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Louise Lantier
- Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA
- Vanderbilt Mouse Metabolic Phenotyping Center, Nashville, TN, USA
| | - Sun H. Peck
- Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Department of Biomedical Engineering, Vanderbilt University School of Engineering, Nashville, TN, USA
- Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN, USA
| | - Katie C. Coate
- Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Roland W. Stein
- Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Nancy Carrasco
- Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Erin S. Calipari
- Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA
- Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN, USA
| | - Melanie R. McReynolds
- Department of Biochemistry and Molecular Biology, Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA
| | - Elma Zaganjor
- Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA
- Vanderbilt Digestive Disease Research Center, Vanderbilt University Medical Center, Nashville, TN, USA
- Vanderbilt Diabetes Research and Training Center, Vanderbilt University Medical Center, Nashville, TN, USA
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16
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Alassiri M, Alanazi A, Barhoumi T, Alrfaei B, Alanazi M, Rashid M, Alhazmi AS, Alasseiri M, AlMefleh A, Boudjelal M, Shaibah H, Almuhalhil K, Mansour FA, Alehaideb Z, Alghanem B. Preliminary findings on the absence of PEPITEM release in B cells isolated from Saudi donors: implications for expanded population studies. AMERICAN JOURNAL OF CLINICAL AND EXPERIMENTAL IMMUNOLOGY 2024; 13:215-225. [PMID: 39583342 PMCID: PMC11578804 DOI: 10.62347/xnno3661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Accepted: 10/08/2024] [Indexed: 11/26/2024]
Abstract
BACKGROUND Adiponectin (AQ) plays a role in regulating immune responses. Previous research indicates that B cells can affect T cell transmigration via the adiponectin-induced peptide PEPITEM in Caucasians. This study explores whether this mechanism is also applicable to Saudi populations, considering potential ethnic variations in immune response. METHODS We conducted unbiased peptidomic screen on B cells, NK cells, and monocytes isolated from the peripheral blood of male healthy Saudi donors. The cells were stimulated with AQ, and the secretion of PEPITEM and other peptides was assessed using liquid chromatography-mass spectrometry (LC-MS/MS). Flow cytometry was utilized to confirm the purity of isolated cell populations and to verify the expression of adiponectin receptors AR1 and AR2. RESULTS PEPITEM was not detected in the supernatants of AQ-stimulated B cells, NK cells, or monocytes. All three cell populations were isolated and purified with high purity, confirmed by flow cytometry showing AR1 and AR2 expression on the surface of these cells. Specifically, less than 47% of B cells expressed ARs, with AR1 at 12% and AR2 at 17%. AQ stimulation increased the number of identified peptides in B cells and monocytes but decreased peptide numbers in NK cells. Dimensionality reduction analysis demonstrated clear segregation of cell types, with strong reproducibility across technical replicates. CONCLUSION The inability of B cells to release PEPITEM in response to AQ stimulation is an interesting finding and it needs more confirmatory tests and experiments, however; a hypothesis about the impact of predisposing factors, such as ethnicity could be formulated and tested in the future.
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Affiliation(s)
- Mohammed Alassiri
- Department of Basic Sciences, College of Science and Health Professions, King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS)Riyadh, KSA
- Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City (KAMC)Riyadh, KSA
| | - Asma Alanazi
- Department of Basic Medical Sciences, College of Medicine, King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City (KAMC)Riyadh, KSA
| | - Tlili Barhoumi
- Medical Research Core Facility and Platforms, King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA)Riyadh, KSA
| | - Bahauddeen Alrfaei
- Department of Basic Medical Sciences, College of Medicine, King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City (KAMC)Riyadh, KSA
- Department of Cellular Therapy and Cancer Research, King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA)Riyadh, KSA
| | - Maisa Alanazi
- Department of Cellular Therapy and Cancer Research, King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA)Riyadh, KSA
| | - Mamoon Rashid
- Department of AI and Bioinformatics, King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA)Riyadh, KSA
| | - Aiman S Alhazmi
- Department of Basic Sciences, College of Science and Health Professions, King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS)Riyadh, KSA
- Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City (KAMC)Riyadh, KSA
| | - Mohammed Alasseiri
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Prince Fahad Bin Sultan Chair for Biomedical Research, University of TabukTabuk, KSA
| | - Abdulrahman AlMefleh
- Department of Radiology, King Faisal Specialist Hospital and Research CenterRiyadh, Saudi Arabia
| | - Mohammad Boudjelal
- Medical Research Core Facility and Platforms, King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA)Riyadh, KSA
| | - Hayat Shaibah
- Medical Research Core Facility and Platforms, King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA)Riyadh, KSA
| | - Khawlah Almuhalhil
- Medical Research Core Facility and Platforms, King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA)Riyadh, KSA
| | - Fatmah A Mansour
- Medical Research Core Facility and Platforms, King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA)Riyadh, KSA
| | - Zeyad Alehaideb
- Medical Research Core Facility and Platforms, King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA)Riyadh, KSA
| | - Bandar Alghanem
- Medical Research Core Facility and Platforms, King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA)Riyadh, KSA
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17
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Li X, Zhuang R, Lu Z, Wu F, Wu X, Zhang K, Wang M, Li W, Zhang H, Zhu W, Zhang B. Nobiletin promotes lipolysis of white adipose tissue in a circadian clock-dependent manner. J Nutr Biochem 2024; 132:109696. [PMID: 39094217 DOI: 10.1016/j.jnutbio.2024.109696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 06/23/2024] [Accepted: 06/25/2024] [Indexed: 08/04/2024]
Abstract
Nobiletin has been reported to protect against obesity-related metabolic disorders by enhancing the circadian rhythm; however its effects on lipid metabolism in adipose tissue are unclear. In this study, mice were fed with high-fat diet (HFD) for four weeks firstly and gavaged with 50 or 200 mg/kg bodyweight/day nobiletin at Zeitgeber time (ZT) 4 for another four weeks while still receiving HFD. At the end of the 8-week experimental period, the mice were sacrificed at ZT4 or ZT8 on the same day. Mature 3T3-L1 adipocytes were treated with nobiletin in the presence or absence of siBmal1, siRora, siRorc, SR8278 or SR9009. Nobiletin reduced the weight of white adipose tissue (WAT) and the size of adipocytes in WAT. At ZT4, nobiletin decreased the TG, TC and LDL-c levels and increased serum FFA level and glucose tolerance. Nobiletin triggered the lipolysis of mesenteric and epididymal WAT at both ZT4 and ZT16. Nobiletin increased the level of RORγ at ZT16, that of BMAL1 and PPARγ at ZT4, and that of ATGL at both ZT4 and ZT16. Nobiletin increased lipolysis and ATGL levels in 3T3-L1 adipocytes in Bmal1- or Rora/c- dependent manner. Dual luciferase assay indicated that nobiletin enhanced the transcriptional activation of RORα/γ on Atgl promoter and decreased the repression of RORα/γ on PPARγ-binding PPRE. Promoter deletion analysis indicated that nobiletin inhibited the suppression of PPARγ-mediated Atgl transcription by RORα/γ. Taken together, nobiletin elevated lipolysis in WAT by increasing ATGL levels through activating the transcriptional activity of RORα/γ and decreasing the repression of RORα/γ on PPARγ-binding PPRE.
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MESH Headings
- Animals
- Flavones/pharmacology
- Lipolysis/drug effects
- Mice
- Adipose Tissue, White/metabolism
- Adipose Tissue, White/drug effects
- 3T3-L1 Cells
- Male
- Circadian Clocks/drug effects
- Mice, Inbred C57BL
- ARNTL Transcription Factors/metabolism
- ARNTL Transcription Factors/genetics
- Diet, High-Fat/adverse effects
- PPAR gamma/metabolism
- PPAR gamma/genetics
- Nuclear Receptor Subfamily 1, Group F, Member 1/metabolism
- Nuclear Receptor Subfamily 1, Group F, Member 1/genetics
- Adipocytes/drug effects
- Adipocytes/metabolism
- Lipase/metabolism
- Obesity/metabolism
- Obesity/drug therapy
- Acyltransferases
- Nuclear Receptor Subfamily 1, Group F, Member 3
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Affiliation(s)
- Xudong Li
- Food Safety and Health Research Center, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China; Department of Toxicological and Biochemical Test, Guangzhou Center for Disease Control and Prevention, Guangzhou, Guangdong, China
| | - Runxuan Zhuang
- Food Safety and Health Research Center, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
| | - Zhitian Lu
- Food Safety and Health Research Center, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China; Department of maternity health, Guangzhou Baiyun District Maternal and Child Health Hospital, Guangzhou, Guangdong, China
| | - Fan Wu
- Food Safety and Health Research Center, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
| | - Xiaoli Wu
- Food Safety and Health Research Center, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
| | - Ke Zhang
- Food Safety and Health Research Center, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
| | - Min Wang
- Food Safety and Health Research Center, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China
| | - Wenxue Li
- Department of Toxicological and Biochemical Test, Guangzhou Center for Disease Control and Prevention, Guangzhou, Guangdong, China
| | - Huijie Zhang
- Department of Endocrinology and Metabolism, Guangdong Provincial Key Laboratory of Shock and Microcirculation, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Wei Zhu
- Department of Toxicological and Biochemical Test, Guangzhou Center for Disease Control and Prevention, Guangzhou, Guangdong, China.
| | - Bo Zhang
- Food Safety and Health Research Center, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China.
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18
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Paixão de Gois B, Figueiredo N, Soares Lopes KL, Esselin de Melo PR, Horst MA, Molin Netto BD, Oyama LM, Lima GC, Dâmaso AR, Mota JF, Corgosinho FC. The impact of the obesity onset on the inflammatory and glycemic profile of women with severe obesity. Surg Obes Relat Dis 2024; 20:976-983. [PMID: 38862297 DOI: 10.1016/j.soard.2024.04.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 04/04/2024] [Accepted: 04/14/2024] [Indexed: 06/13/2024]
Abstract
BACKGROUND The stage of life at the onset of obesity is an important factor in assessing inflammatory state and cardiometabolic risk. OBJECTIVES This study aimed to evaluate the relationship between the obesity onset and the inflammatory profile in women with severe obesity. SETTING Public hospital, Brazil. METHODS Forty-eight women with severe obesity (20-59 yr old) were evaluated according to weight, height, neck circumference (NC), waist circumference (WC), and hip circumference, as well blood metabolic and inflammatory parameters. The participants were grouped according to obesity onset stage of life (early group: ≤19 yr; late group: >19 yr). RESULTS The demographic means of the participants were: age of 39.7 years, weight of 122.7 kg and body mass index (BMI) of 48.4 kg/m2. The late group presented significantly higher values of leptin (lep)/adiponectin (adipo) ratio and homeostatic model assessment for insulin resistance (HOMA-IR) than the early group. The late group also had a lower adipo/lep ratio. Moreover, the late group showed correlations between the lep/adipo ratio and BMI (r = .460, P = .021), NC (r = .478, P = .016), and WC (r = .535, P = .006). Adipo was also correlated with NC (r = -.418, P = .038), WC (r = -.437, P = .029), and glycated hemoglobin (HbA1C) (r = -.485, P = .019). By contrast, in the early group, the lep/adipo ratio showed correlations with insulin (r = .647, P = .004) and HOMA-B (r = .564, P = .015). CONCLUSIONS The inflammatory profile is correlated with anthropometric values in women with late-onset obesity. Inflammatory markers seemed to correlate with the glycemic profile in women with early-onset obesity. Furthermore, inflammation was higher in women with late-onset obesity compared to those with early-onset obesity.
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Affiliation(s)
| | - Nayra Figueiredo
- Faculty of Medicine, Federal University of Goiás, Goiânia, Brazil
| | | | | | - Maria Aderuza Horst
- Post-Graduation Program in Nutrition and Health, Federal University of Goiás, Goiânia, Brazil
| | | | - Lila Missae Oyama
- Paulista Medicine School, Federal University of São Paulo, São Paulo, Brazil
| | - Glaucia Carielo Lima
- Post-Graduation Program in Nutrition and Health, Federal University of Goiás, Goiânia, Brazil
| | - Ana Raimunda Dâmaso
- Paulista Medicine School, Federal University of São Paulo, São Paulo, Brazil
| | - Joao Felipe Mota
- Faculty of Nutrition, Federal University of Goiás, Goiânia, Brazil
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Ali M, Longet S, Neale I, Rongkard P, Chowdhury FUH, Hill J, Brown A, Laidlaw S, Tipton T, Hoque A, Hassan N, Hackstein CP, Adele S, Akther HD, Abraham P, Paul S, Rahman MM, Alam MM, Parvin S, Mollah FH, Hoque MM, Moore SC, Biswas SK, Turtle L, de Silva TI, Ogbe A, Frater J, Barnes E, Tomic A, Carroll MW, Klenerman P, Kronsteiner B, Chowdhury FR, Dunachie SJ. Obesity differs from diabetes mellitus in antibody and T-cell responses post-COVID-19 recovery. Clin Exp Immunol 2024; 218:78-92. [PMID: 38642547 PMCID: PMC11404124 DOI: 10.1093/cei/uxae030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Revised: 01/05/2024] [Accepted: 04/18/2024] [Indexed: 04/22/2024] Open
Abstract
OBJECTIVE Obesity and type 2 diabetes (DM) are risk factors for severe coronavirus disease 2019 (COVID-19) outcomes, which disproportionately affect South Asian populations. This study aims to investigate the humoral and cellular immune responses to SARS-CoV-2 in adult COVID-19 survivors with overweight/obesity (Ov/Ob, BMI ≥ 23 kg/m2) and DM in Bangladesh. METHODS In this cross-sectional study, SARS-CoV-2-specific antibody and T-cell responses were investigated in 63 healthy and 75 PCR-confirmed COVID-19 recovered individuals in Bangladesh, during the pre-vaccination first wave of the COVID-19 pandemic in 2020. RESULTS In COVID-19 survivors, SARS-CoV-2 infection induced robust antibody and T-cell responses, which correlated with disease severity. After adjusting for age, sex, DM status, disease severity, and time since onset of symptoms, Ov/Ob was associated with decreased neutralizing antibody titers, and increased SARS-CoV-2 spike-specific IFN-γ response along with increased proliferation and IL-2 production by CD8 + T cells. In contrast, DM was not associated with SARS-CoV-2-specific antibody and T-cell responses after adjustment for obesity and other confounders. CONCLUSION Ov/Ob is associated with lower neutralizing antibody levels and higher T-cell responses to SARS-CoV-2 post-COVID-19 recovery, while antibody or T-cell responses remain unaltered in DM.
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Affiliation(s)
- Mohammad Ali
- Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
- Centre for Global Health Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
- Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand
- Directorate General of Health Services, Dhaka, Bangladesh
- Department of Biochemistry and Molecular Biology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Stephanie Longet
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Isabel Neale
- Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
- Centre for Global Health Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
- Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand
| | - Patpong Rongkard
- Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
- Centre for Global Health Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
- Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand
| | | | - Jennifer Hill
- Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
- Centre for Global Health Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
- Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand
| | - Anthony Brown
- Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
| | - Stephen Laidlaw
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Tom Tipton
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Ashraful Hoque
- Department of Transfusion Medicine, Sheikh Hasina National Burn & Plastics Surgery Institute, Dhaka, Bangladesh
| | - Nazia Hassan
- Department of Internal Medicine, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Carl-Philipp Hackstein
- Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
- Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
| | - Sandra Adele
- Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
- Centre for Global Health Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
- Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand
| | - Hossain Delowar Akther
- Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
- Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
| | - Priyanka Abraham
- Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
- Centre for Global Health Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
- Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand
| | - Shrebash Paul
- Department of Internal Medicine, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Md Matiur Rahman
- Department of Biochemistry and Molecular Biology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Md Masum Alam
- Department of Biochemistry and Molecular Biology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Shamima Parvin
- Department of Biochemistry and Molecular Biology, Mugda Medical College, Dhaka, Bangladesh
| | - Forhadul Hoque Mollah
- Department of Biochemistry and Molecular Biology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Md Mozammel Hoque
- Department of Biochemistry and Molecular Biology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Shona C Moore
- Tropical and Infectious Disease Unit, Liverpool University Hospitals NHS Foundation Trust, Member of Liverpool Health Partners, Liverpool, UK
| | - Subrata K Biswas
- Department of Biochemistry and Molecular Biology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
- Department of Molecular and Cell Biology, University of Connecticut, Storrs, Connecticut, USA
| | - Lance Turtle
- Tropical and Infectious Disease Unit, Liverpool University Hospitals NHS Foundation Trust, Member of Liverpool Health Partners, Liverpool, UK
| | - Thushan I de Silva
- Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
| | - Ane Ogbe
- Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
| | - John Frater
- Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
| | - Eleanor Barnes
- Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
- Centre for Global Health Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
- NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Adriana Tomic
- National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA
- Department of Microbiology, Boston University School of Medicine, Boston, MA, USA
- Department of Biomedical Engineering, Boston University, Boston, MA, USA
| | - Miles W Carroll
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Paul Klenerman
- Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
- Centre for Global Health Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
- Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
- NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Barbara Kronsteiner
- Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
- Centre for Global Health Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
- Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand
| | - Fazle Rabbi Chowdhury
- Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand
- Department of Internal Medicine, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Susanna J Dunachie
- Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
- Centre for Global Health Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
- Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand
- NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
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20
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Hu F, Yu Y, Xu H. How does exosome cause diabetes? Hormones (Athens) 2024; 23:385-393. [PMID: 38233729 DOI: 10.1007/s42000-024-00525-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Accepted: 01/08/2024] [Indexed: 01/19/2024]
Abstract
Exosomes are extracellular vesicles that are widely distributed in multiple cell types and circulating body fluids. They have a specific effect on the target cells by releasing different vesicle contents. They have recently been recognized as important means of intercellular communication, being involved, for example, in the development of diabetes by increasing β-cell apoptosis, activating autoimmunity, and regulating cytokines to affect islet β-cell function and insulin sensitivity. An in-depth study of the role of exosome in the pathogenesis of diabetes may therefore provide a novel means of diagnosing and treating diabetes. In this review, we detail how exosome is involved in the development of diabetes.
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Affiliation(s)
- Fei Hu
- Cixi Biomedical Research Institute, Wenzhou Medical University, Cixi, Ningbo, China
| | - Yicong Yu
- Zhejiang Center of Animal Disease Control, Hangzhou, China
| | - Hongming Xu
- Department of Orthopaedic Surgery, Affiliated Cixi Hospital, Wenzhou Medical University, No. 999, South Second Ring Road, Hushan Street, Cixi, Ningbo, 315300, China.
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21
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Frąk M, Grenda A, Krawczyk P, Kuźnar-Kamińska B, Pazdrowski P, Kędra K, Chmielewska I, Milanowski J. The influence of nutritional status, lipid profile, leptin concentration and polymorphism of genes encoding leptin and neuropeptide Y on the effectiveness of immunotherapy in advanced NSCLC patients. BMC Cancer 2024; 24:937. [PMID: 39090596 PMCID: PMC11295594 DOI: 10.1186/s12885-024-12716-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Accepted: 07/26/2024] [Indexed: 08/04/2024] Open
Abstract
INTRODUCTION Neuropeptide Y is a neurotransmitter in the nervous system and belongs to the orexigenic system that increases appetite. Its excessive secretion leads to obesity. Leptin is a pro-inflammatory adipokine (produced in adipose tissue) induced in obesity and may mediate increased antitumor immunity in obesity (including the promotion of M1 macrophages). Leptin and neuropeptide Y gene polymorphisms, causing increased leptin levels and the occurrence of obesity, and lipid profile disorders, may increase the effectiveness of immunotherapy. MATERIALS AND METHODS In 121 patients with advanced NSCLC without mutations in the EGFR gene and rearrangements of the ALK and ROS1 genes, undergoing immunotherapy (1st and 2nd line of treatment) or chemoimmunotherapy (1st line of treatment), we assessed BMI, lipid profile, PD-L1 expression on cancer cells using the immunohistochemical method (clone SP263 antibody), leptin concentration in blood serum by ELISA, polymorphisms in the promoter region of the genes for leptin (LEP) and neuropeptide Y (NPY) by real-time PCR. RESULTS Leptin concentration was significantly higher in obese patients than in patients with normal or low weight (p = 0.00003) and in patients with disease stabilization compared to patients with progression observed during immunotherapy (p = 0.012). Disease control occurred significantly more often in patients with the GA or AA genotype than patients with the GG genotype in the rs779039 polymorphism of the LEP gene. The median PFS in the entire study group was five months (95% CI: 3-5.5), and the median OS was 12 months (95% CI: 8-16). Median PFS was highest in patients with TPS ≥ 50% (6.5 months) and in obese patients (6.6 months). Obese patients also had a slightly longer median OS compared to other patients (23.8 vs. 13 months). The multivariate Cox logistic regression test showed that the only factor reducing the risk of progression was TPS ≥ 50% (HR = 0.6068, 95% CI: 0.4001-0.9204, p = 0, 0187), and the only factor reducing the risk of death was high leptin concentration (HR = 0.6743, 95% CI: 0.4243-1.0715, p = 0.0953). CONCLUSION Assessment of nutritional status, serum leptin concentration and polymorphisms in the LEP gene may be of additional importance in predicting the effectiveness of immunotherapy and chemoimmunotherapy in patients with advanced NSCLC.
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Affiliation(s)
- Małgorzata Frąk
- Department of Pneumonology, Oncology and Allergology Medical, University of Lublin, Jaczewskiego 8, Lublin, 20-954, Poland.
| | - Anna Grenda
- Department of Pneumonology, Oncology and Allergology Medical, University of Lublin, Jaczewskiego 8, Lublin, 20-954, Poland.
| | - Paweł Krawczyk
- Department of Pneumonology, Oncology and Allergology Medical, University of Lublin, Jaczewskiego 8, Lublin, 20-954, Poland
| | - Barbara Kuźnar-Kamińska
- Department of Pulmonology, Allergology and Pulmonary Oncology, Poznan University of Medical Sciences, Poznań, Poland
| | - Paweł Pazdrowski
- Department of Head, Neck Surgery and Laryngological Oncology, Poznan University of Medical Sciences, Poznań, Poland
| | - Karolina Kędra
- Institute of Physical Chemistry, Polish Academy of Sciences in Warsaw, Warsaw, Poland
| | - Izabela Chmielewska
- Department of Pneumonology, Oncology and Allergology Medical, University of Lublin, Jaczewskiego 8, Lublin, 20-954, Poland
| | - Janusz Milanowski
- Department of Pneumonology, Oncology and Allergology Medical, University of Lublin, Jaczewskiego 8, Lublin, 20-954, Poland
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22
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Reddy A, Deo KS, Pillai NS, Patil P, Chaurasia P, Puttur N, Lakhey K. A Study of Prevalence of Metabolic Syndrome in Premenopausal Women With Female Pattern Hair Loss: A Case-Control Study. Cureus 2024; 16:e68039. [PMID: 39347162 PMCID: PMC11433530 DOI: 10.7759/cureus.68039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Accepted: 08/28/2024] [Indexed: 10/01/2024] Open
Abstract
Background and objective Female pattern hair loss (FPHL), also known as androgenetic alopecia (AGA), is a condition where the hair follicles of genetically susceptible women gradually shrink and become thinner, leading to hair loss in a particular pattern. Metabolic syndrome (MS) is a collection of conditions that co-occur, increasing the risk of heart disease, stroke, and type 2 diabetes. This study aims to determine the prevalence of MS in premenopausal women in patients with FPHL. Methods and materials We conducted a case-control, hospital-based observational study at our institution for a period of two years, which included 62 patients, with 31 cases (patients with FPHL) and 31 controls (patients without FPHL). Results In some cases, the mean age was 29.81 years, while in controls, it was 28.84 years. The mean waist circumference (WC) in cases was 81.9 +/- 11.75 cm, and in controls, it was 72.65 +/- 8.86 cm, with a statistically significant p-value of 0.001. In some cases, the mean body mass index (BMI) was 26.28 +/- 4.09 kg/m2, and in controls, it was 24.52 +/- 2.78 kg/m2, with a statistically significant p-value of 0.013. Between cases and controls, there was no significant difference in the homeostatic model assessment of insulin resistance (HOMA-IR), fasting blood glucose (FBG), fasting triglyceride levels, fasting HDL, and fasting insulin levels. Conclusion The study found a significant association between WC and BMI in patients with FPHL in premenopausal women. This highlights the need for early screening and preventive measures for MS in women presenting with FPHL.
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Affiliation(s)
- Aravind Reddy
- Dermatology, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, IND
| | - Kirti S Deo
- Dermatology, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, IND
| | - Niranjana S Pillai
- Dermatology, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, IND
| | - Priyanka Patil
- Dermatology, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, IND
| | - Pooja Chaurasia
- Dermatology, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, IND
| | - Namratha Puttur
- Dermatology, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, IND
| | - Kshitiz Lakhey
- Dermatology, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, IND
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23
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Wu Y, Sun Y, Song Y, Wang J, Han Y, Yang N, Lin H, Yin Y, Han X. PPA1 promotes adipogenesis by regulating the stability of C/EBPs. Cell Death Differ 2024; 31:1044-1056. [PMID: 38762596 PMCID: PMC11303681 DOI: 10.1038/s41418-024-01309-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 04/24/2024] [Accepted: 05/01/2024] [Indexed: 05/20/2024] Open
Abstract
Adipogenesis significantly contributes to healthy adipose tissue expansion in obesity. Increasing adipocyte number or function to alleviate adipose tissue overload could serve as a therapeutic strategy for both lipodystrophy and obesity-related metabolic syndrome. Inorganic pyrophosphatase (PPA1) is an enzyme that catalyzes the hydrolysis of pyrophosphate (PPi) and is involved in many biochemical reactions, but its function in adipose tissue has not been studied previously. In this study, we demonstrated that adipose-specific PPA1 knockout (PPA1AKO) mice showed lipodystrophy and spontaneously developed hepatic steatosis and severe insulin resistance under normal chow diet feeding. PPA1 deficiency suppressed the differentiation of primary adipocyte precursors and 3T3-L1 cells. Notably, PPA1 overexpression can restore inhibited adipogenesis in preadipocytes isolated from db/db mice and type 2 diabetes patients. Mechanistic studies have revealed that PPA1 acts as a positive regulator of early adipocyte differentiation by promoting CCAAT/enhancer-binding proteinβ and δ (C/EBPβ and δ) protein stability. Moreover, the function of PPA1 in adipogenesis is independent of its PPi catalytic activity. Collectively, our in vivo and in vitro findings demonstrated that PPA1 is a novel critical upstream regulator of adipogenesis, controlling adipose tissue development and whole-body metabolic homeostasis.
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Affiliation(s)
- Yangyang Wu
- Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, China
- Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing Medical University, Nanjing, China
| | - Yue Sun
- Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Yuqing Song
- Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Jiateng Wang
- Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Ye Han
- Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Nan Yang
- Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Haiyan Lin
- Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
| | - Ye Yin
- Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
| | - Xiao Han
- Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
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Savulescu-Fiedler I, Mihalcea R, Dragosloveanu S, Scheau C, Baz RO, Caruntu A, Scheau AE, Caruntu C, Benea SN. The Interplay between Obesity and Inflammation. Life (Basel) 2024; 14:856. [PMID: 39063610 PMCID: PMC11277997 DOI: 10.3390/life14070856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 07/01/2024] [Accepted: 07/05/2024] [Indexed: 07/28/2024] Open
Abstract
Obesity is an important condition affecting the quality of life of numerous patients and increasing their associated risk for multiple diseases, including tumors and immune-mediated disorders. Inflammation appears to play a major role in the development of obesity and represents a central point for the activity of cellular and humoral components in the adipose tissue. Macrophages play a key role as the main cellular component of the adipose tissue regulating the chronic inflammation and modulating the secretion and differentiation of various pro- and anti-inflammatory cytokines. Inflammation also involves a series of signaling pathways that might represent the focus for new therapies and interventions. Weight loss is essential in decreasing cardiometabolic risks and the degree of associated inflammation; however, the latter can persist for long after the excess weight is lost, and can involve changes in macrophage phenotypes that can ensure the metabolic adjustment. A clear understanding of the pathophysiological processes in the adipose tissue and the interplay between obesity and chronic inflammation can lead to a better understanding of the development of comorbidities and may ensure future targets for the treatment of obesity.
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Affiliation(s)
- Ilinca Savulescu-Fiedler
- Department of Internal Medicine, The “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Internal Medicine and Cardiology, Coltea Clinical Hospital, 030167 Bucharest, Romania
| | - Razvan Mihalcea
- Department of Internal Medicine and Cardiology, Coltea Clinical Hospital, 030167 Bucharest, Romania
| | - Serban Dragosloveanu
- Department of Orthopaedics, “Foisor” Clinical Hospital of Orthopaedics, Traumatology and Osteoarticular TB, 021382 Bucharest, Romania
- Department of Orthopaedics and Traumatology, The “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Cristian Scheau
- Department of Physiology, The “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania (C.C.)
- Department of Radiology and Medical Imaging, “Foisor” Clinical Hospital of Orthopaedics, Traumatology and Osteoarticular TB, 030167 Bucharest, Romania
| | - Radu Octavian Baz
- Clinical Laboratory of Radiology and Medical Imaging, “Sf. Apostol Andrei” County Emergency Hospital, 900591 Constanta, Romania
- Department of Radiology and Medical Imaging, Faculty of Medicine, “Ovidius” University, 900527 Constanta, Romania
| | - Ana Caruntu
- Department of Oral and Maxillofacial Surgery, “Carol Davila” Central Military Emergency Hospital, 010825 Bucharest, Romania
- Department of Oral and Maxillofacial Surgery, Faculty of Dental Medicine, “Titu Maiorescu” University, 031593 Bucharest, Romania
| | - Andreea-Elena Scheau
- Department of Radiology and Medical Imaging, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Constantin Caruntu
- Department of Physiology, The “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania (C.C.)
- Department of Dermatology, “Prof. N.C. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, 011233 Bucharest, Romania
| | - Serban Nicolae Benea
- Department of Infectious Diseases, The “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- “Prof. Dr. Matei Balș” National Institute for Infectious Diseases, 021105 Bucharest, Romania
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25
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Khan MM, Khan ZA, Khan MA. Metabolic complications of psychotropic medications in psychiatric disorders: Emerging role of de novo lipogenesis and therapeutic consideration. World J Psychiatry 2024; 14:767-783. [PMID: 38984346 PMCID: PMC11230099 DOI: 10.5498/wjp.v14.i6.767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Revised: 05/05/2024] [Accepted: 05/23/2024] [Indexed: 06/19/2024] Open
Abstract
Although significant advances have been made in understanding the patho-physiology of psychiatric disorders (PDs), therapeutic advances have not been very convincing. While psychotropic medications can reduce classical symptoms in patients with PDs, their long-term use has been reported to induce or exaggerate various pre-existing metabolic abnormalities including diabetes, obesity and non-alcoholic fatty liver disease (NAFLD). The mechanism(s) underlying these metabolic abnormalities is not clear; however, lipid/fatty acid accumulation due to enhanced de novo lipogenesis (DNL) has been shown to reduce membrane fluidity, increase oxidative stress and inflammation leading to the development of the aforementioned metabolic abnormalities. Intriguingly, emerging evidence suggest that DNL dysregulation and fatty acid accumulation could be the major mechanisms associated with the development of obesity, diabetes and NAFLD after long-term treatment with psychotropic medications in patients with PDs. In support of this, several adjunctive drugs comprising of anti-oxidants and anti-inflammatory agents, that are used in treating PDs in combination with psychotropic medications, have been shown to reduce insulin resistance and development of NAFLD. In conclusion, the above evidence suggests that DNL could be a potential pathological factor associated with various metabolic abnormalities, and a new avenue for translational research and therapeutic drug designing in PDs.
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Affiliation(s)
- Mohammad M Khan
- Laboratory of Translational Neurology and Molecular Psychiatry, Department of Biotechnology, Era’s Lucknow Medical College and Hospital, and Faculty of Science, Era University, Lucknow 226003, India
| | - Zaw Ali Khan
- Era’s Lucknow Medical College and Hospital, Era University, Lucknow 226003, India
| | - Mohsin Ali Khan
- Era’s Lucknow Medical College and Hospital, Era University, Lucknow 226003, India
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26
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Bradshaw T, Simmons C, Ott RK, Armstrong AR. Ras/MAPK signaling mediates adipose tissue control of ovarian germline survival and ovulation in Drosophila melanogaster. Dev Biol 2024; 510:17-28. [PMID: 38423203 DOI: 10.1016/j.ydbio.2024.02.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Revised: 02/22/2024] [Accepted: 02/26/2024] [Indexed: 03/02/2024]
Abstract
From insects to humans, oogenesis is tightly linked to nutritional input, yet little is known about how whole organism physiology matches dietary changes with oocyte development. Considering that diet-induced adipose tissue dysfunction is associated with an increased risk for fertility problems, and other obesity-associated pathophysiologies, it is critical to decipher the cellular and molecular mechanisms linking adipose nutrient sensing to remote control of the ovary and other tissues. Our previous studies in Drosophila melanogaster have shown that amino acid sensing, via the amino acid response pathway and mTOR-mediated signaling function within adipocytes to control germline stem cell maintenance and ovulation, respectively. Additionally, we demonstrated that insulin/insulin-like growth factor signaling within adipocytes employs distinct effector axes, PI3K/Akt1-dependent and -independent, downstream of insulin receptor activity to mediate fat-to-ovary communication. Here, we report that the Ras/MAPK signaling axis functions in adipocytes to regulate early germline cyst survival and ovulation of mature oocytes but is not important for germline stem cell maintenance or the progression through vitellogenesis. Thus, these studies uncover the complexity of signaling pathway activity that mediates inter-organ communication.
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Affiliation(s)
- Tancia Bradshaw
- University of South Carolina, Department of Biological Sciences, Columbia, SC, USA
| | - Chad Simmons
- University of South Carolina, Department of Biological Sciences, Columbia, SC, USA
| | - Rachael K Ott
- University of South Carolina, Department of Biological Sciences, Columbia, SC, USA
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27
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Xiao K, Chen L, Mao Y, Bao H, Chen W, Li X, Wu Y. Expression of visfatin in gingival crevicular fluid and gingival tissues in different periodontal conditions: a cross-sectional study. BMC Oral Health 2024; 24:514. [PMID: 38698364 PMCID: PMC11064311 DOI: 10.1186/s12903-024-04299-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2024] [Accepted: 04/26/2024] [Indexed: 05/05/2024] Open
Abstract
BACKGROUND Studies have shown that visfatin is an inflammatory factor closely related to periodontitis. We examined the levels of visfatin in gingival crevicular fluid (GCF) and gingival tissues under different periodontal conditions, in order to provide more theoretical basis for exploring the role of visfatin in the pathogenesis of periodontitis. METHODS We enrolled 87 subjects, with 43 in the chronic periodontitis (CP) group, 21 in the chronic gingivitis (CG) group, and 23 in the periodontal health (PH) group. Periodontal indexes (PD, AL, PLI, and BI) were recorded. GCF samples were collected for visfatin quantification, and gingival tissues were assessed via immunohistochemical staining. RESULTS Visfatin levels in GCF decreased sequentially from CP to CG and PH groups, with statistically significant differences (P < 0.05). The CP group exhibited the highest visfatin levels, while the PH group had the lowest. Gingival tissues showed a similar trend, with significant differences between groups (P < 0.001). Periodontal indexes were positively correlated with visfatin levels in both GCF and gingival tissues (P < 0.001). A strong positive correlation was observed between visfatin levels in GCF and gingival tissues (rs = 0.772, P < 0.001). CONCLUSION Greater periodontal destruction corresponded to higher visfatin levels in GCF and gingival tissues, indicating their potential collaboration in damaging periodontal tissues. Visfatin emerges as a promising biomarker for periodontitis and may play a role in its pathogenesis.
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Affiliation(s)
- Kang Xiao
- Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key Lab of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China
- Institute of Stomatology & Research Center of Dental and Craniofacial Implants, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China
| | - Ling Chen
- Stomatological Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Stomatological Center, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China
| | - Yudian Mao
- Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key Lab of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China
- Institute of Stomatology & Research Center of Dental and Craniofacial Implants, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China
| | - Han Bao
- Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key Lab of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China
- Institute of Stomatology & Research Center of Dental and Craniofacial Implants, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China
| | - Weirong Chen
- Stomatological Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Stomatological Center, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China
| | - Xiang Li
- Stomatological Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Stomatological Center, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China
| | - Yun Wu
- Stomatological Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
- Stomatological Center, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China.
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Haneishi Y, Treppiccione L, Maurano F, Luongo D, Miyamoto J, Rossi M. High Fat Diet-Wheat Gliadin Interaction and its Implication for Obesity and Celiac Disease Onset: In Vivo Studies. Mol Nutr Food Res 2024; 68:e2300779. [PMID: 38632845 DOI: 10.1002/mnfr.202300779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 03/03/2024] [Indexed: 04/19/2024]
Abstract
The intestinal immune system plays a crucial role in obesity and insulin resistance. An altered intestinal immunity is associated with changes to the gut microbiota, barrier function, and tolerance to luminal antigens. Lipid metabolism and its unbalance can also contribute to acute and chronic inflammation in different conditions. In celiac disease (CD), the serum phospholipid profile in infants who developed CD is dramatically different when compared to that of infants at risk of CD not developing the disease. In a mouse model of gluten sensitivity, oral wheat gliadin challenge in connection with inhibition of the metabolism of arachidonic acid, an omega-6 polyunsaturated fatty acid, specifically induces the enteropathy. Recent evidence suggests that gluten may play a role also for development of life-style related diseases in populations on a high fat diet (HFD). However, the mechanisms behind these effects are not yet understood. Exploratory studies in mice feed HFD show that wheat gliadin consumption affects glucose and lipid metabolic homeostasis, alters the gut microbiota, and the immune cell profile in liver.
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Affiliation(s)
- Yuri Haneishi
- Department of Applied Biological Science, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Fuchu-shi, Tokyo, 183-8509, Japan
| | | | - Francesco Maurano
- Institute of Food Sciences, CNR, via Roma 64, Avellino, 83100, Italy
| | - Diomira Luongo
- Institute of Food Sciences, CNR, via Roma 64, Avellino, 83100, Italy
| | - Junki Miyamoto
- Department of Applied Biological Science, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Fuchu-shi, Tokyo, 183-8509, Japan
| | - Mauro Rossi
- Institute of Food Sciences, CNR, via Roma 64, Avellino, 83100, Italy
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29
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Sajic T, Ferreira Gomes CK, Gasser M, Caputo T, Bararpour N, Landaluce-Iturriria E, Augsburger M, Walter N, Hainard A, Lopez-Mejia IC, Fracasso T, Thomas A, Gilardi F. SMYD3: a new regulator of adipocyte precursor proliferation at the early steps of differentiation. Int J Obes (Lond) 2024; 48:557-566. [PMID: 38148333 PMCID: PMC10978492 DOI: 10.1038/s41366-023-01450-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 12/06/2023] [Accepted: 12/12/2023] [Indexed: 12/28/2023]
Abstract
BACKGROUND In obesity, adipose tissue undergoes a remodeling process characterized by increased adipocyte size (hypertrophia) and number (hyperplasia). The ability to tip the balance toward the hyperplastic growth, with recruitment of new fat cells through adipogenesis, seems to be critical for a healthy adipose tissue expansion, as opposed to a hypertrophic growth that is accompanied by the development of inflammation and metabolic dysfunction. However, the molecular mechanisms underlying the fine-tuned regulation of adipose tissue expansion are far from being understood. METHODS We analyzed by mass spectrometry-based proteomics visceral white adipose tissue (vWAT) samples collected from C57BL6 mice fed with a HFD for 8 weeks. A subset of these mice, called low inflammation (Low-INFL), showed reduced adipose tissue inflammation, as opposed to those developing the expected inflammatory response (Hi-INFL). We identified the discriminants between Low-INFL and Hi-INFL vWAT samples and explored their function in Adipose-Derived human Mesenchymal Stem Cells (AD-hMSCs) differentiated to adipocytes. RESULTS vWAT proteomics allowed us to quantify 6051 proteins. Among the candidates that most differentiate Low-INFL from Hi-INFL vWAT, we found proteins involved in adipocyte function, including adiponectin and hormone sensitive lipase, suggesting that adipocyte differentiation is enhanced in Low-INFL, as compared to Hi-INFL. The chromatin modifier SET and MYND Domain Containing 3 (SMYD3), whose function in adipose tissue was so far unknown, was another top-scored hit. SMYD3 expression was significantly higher in Low-INFL vWAT, as confirmed by western blot analysis. Using AD-hMSCs in culture, we found that SMYD3 mRNA and protein levels decrease rapidly during the adipocyte differentiation. Moreover, SMYD3 knock-down before adipocyte differentiation resulted in reduced H3K4me3 and decreased cell proliferation, thus limiting the number of cells available for adipogenesis. CONCLUSIONS Our study describes an important role of SMYD3 as a newly discovered regulator of adipocyte precursor proliferation during the early steps of adipogenesis.
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Affiliation(s)
- Tatjana Sajic
- Unit of Forensic Toxicology and Chemistry, CURML, Lausanne and Geneva University Hospitals, Lausanne, Geneva, Switzerland
- Faculty Unit of Toxicology, CURML, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
| | | | - Marie Gasser
- Unit of Forensic Toxicology and Chemistry, CURML, Lausanne and Geneva University Hospitals, Lausanne, Geneva, Switzerland
- Faculty Unit of Toxicology, CURML, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
| | - Tiziana Caputo
- Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
| | - Nasim Bararpour
- Stanford Center for Genomics and Personalized Medicine, Stanford, CA, USA
- Department of Genetics, Stanford University, Stanford, CA, USA
| | | | - Marc Augsburger
- Unit of Forensic Toxicology and Chemistry, CURML, Lausanne and Geneva University Hospitals, Lausanne, Geneva, Switzerland
| | - Nadia Walter
- Proteomics Core Facility, Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - Alexandre Hainard
- Proteomics Core Facility, Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | | | - Tony Fracasso
- Unit of Forensic Medicine, CURML, Lausanne and Geneva University Hospitals, Lausanne, Geneva, Switzerland
| | - Aurélien Thomas
- Unit of Forensic Toxicology and Chemistry, CURML, Lausanne and Geneva University Hospitals, Lausanne, Geneva, Switzerland
- Faculty Unit of Toxicology, CURML, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
| | - Federica Gilardi
- Unit of Forensic Toxicology and Chemistry, CURML, Lausanne and Geneva University Hospitals, Lausanne, Geneva, Switzerland.
- Faculty Unit of Toxicology, CURML, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
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30
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Saccaro LF, Aimo A, Panichella G, Sentissi O. Shared and unique characteristics of metabolic syndrome in psychotic disorders: a review. Front Psychiatry 2024; 15:1343427. [PMID: 38501085 PMCID: PMC10944869 DOI: 10.3389/fpsyt.2024.1343427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Accepted: 02/15/2024] [Indexed: 03/20/2024] Open
Abstract
Introduction People with psychosis spectrum disorders (PSD) face an elevated risk of metabolic syndrome (MetS), which may reduce their life expectancy by nearly 20%. Pinpointing the shared and specific characteristics and clinical implications of MetS in PSD is crucial for designing interventions to reduce this risk, but an up-to-date review on MetS across the psychosis spectrum is lacking. Methods This narrative review fills this gap by examining the clinical literature on characteristics and implications of MetS in both distinct PSD and transdiagnostically, i.e., across traditional categorical diagnoses, with a focus on psychiatric and cardio-metabolic management. Results We discuss common and specific characteristics of MetS in PSD, as well as factors contributing to MetS development in PSD patients, including unhealthy lifestyle factors, genetic predisposition, pro-inflammatory state, drugs consumption, antipsychotic medication, and psychotic symptoms. We highlight the importance of early identification and management of cardio-metabolic risk in PSD patients, as well as the existing gaps in the literature, for instance in the screening for MetS in younger PSD patients. We compare hypotheses-generating clinical associations and characteristics of MetS in different PSD, concluding by reviewing the existing recommendations and challenges in screening, monitoring, and managing MetS in PSD. Conclusion Early identification and management of MetS are crucial to mitigate the long-term cardio-metabolic toll in PSD patients. Interventions should focus on healthy lifestyle and appropriate pharmacological and behavioral interventions. Further translational and clinical research is needed to develop targeted interventions and personalized treatment approaches for this vulnerable population, aiming at improving physical health and overall well-being.
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Affiliation(s)
- Luigi F Saccaro
- Psychiatry Department, Faculty of Medicine, University of Geneva, Geneva, Switzerland
- Psychiatry Department, Geneva University Hospital, Geneva, Switzerland
| | - Alberto Aimo
- Interdisciplinary Center for Health Sciences, Scuola Superiore Sant'Anna, Pisa, Italy
- Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy
| | - Giorgia Panichella
- Interdisciplinary Center for Health Sciences, Scuola Superiore Sant'Anna, Pisa, Italy
| | - Othman Sentissi
- Psychiatry Department, Faculty of Medicine, University of Geneva, Geneva, Switzerland
- Psychiatry Department, Geneva University Hospital, Geneva, Switzerland
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31
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Cho SY, Choi JS, Jung UJ. Effects of Ecklonia stolonifera Extract on Metabolic Dysregulation in High-Fat Diet-Induced Obese Mice. J Med Food 2024; 27:242-249. [PMID: 38354279 DOI: 10.1089/jmf.2023.k.0252] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/16/2024] Open
Abstract
This study aimed to test the hypothesis that long-term and low-dose supplementation with an ethanol extract of Ecklonia stolonifera may confer protection against high-fat diet (HFD)-induced obesity in mice. Male C57BL/6J mice were divided into two groups, one of which was fed an HFD (40 kcal% fat) and the other an HFD+E. stolonifera (0.006%, w/w, ∼5 mg/kg body weight/day) for 16 weeks. E. stolonifera supplementation significantly reduced body weight from week 3 and until the end of the experiment. E. stolonifera-supplemented mice also exhibited lower fat mass (epididymal, perirenal, and mesenteric fat) and smaller adipocyte size than HFD control mice. The two groups displayed similar food intakes, but E. stolonifera markedly decreased lipogenesis and increased lipolysis and fatty acid oxidation in adipose tissue. Moreover, E. stolonifera significantly decreased plasma and hepatic lipid levels, hepatic lipid droplet accumulation, plasma aminotransferase levels, and liver weight by decreasing lipogenesis and increasing fatty acid oxidation. As E. stolonifera-supplemented mice showed improvements in hyperglycemia, insulin resistance, and inflammation, compared to control mice, it is possible that the beneficial effects of E. stolonifera on obesity might be associated with decreased inflammation and insulin resistance. Collectively, these results indicate that E. stolonifera could be used as a novel means of preventing and treating obesity and obesity-related metabolic disorders.
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Affiliation(s)
- Su Yeon Cho
- Department of Food Science and Nutrition, Pukyong National University, Busan, Korea
| | - Jae Sue Choi
- Department of Food Science and Nutrition, Pukyong National University, Busan, Korea
| | - Un Ju Jung
- Department of Food Science and Nutrition, Pukyong National University, Busan, Korea
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32
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Abbasi K, Zarezadeh R, Valizadeh A, Mehdizadeh A, Hamishehkar H, Nouri M, Darabi M. White-brown adipose tissue interplay in polycystic ovary syndrome: Therapeutic avenues. Biochem Pharmacol 2024; 220:116012. [PMID: 38159686 DOI: 10.1016/j.bcp.2023.116012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Accepted: 12/22/2023] [Indexed: 01/03/2024]
Abstract
This study highlights the therapeutic potential of activating brown adipose tissue (BAT) for managing polycystic ovary syndrome (PCOS), a prevalent endocrine disorder associated with metabolic and reproductive abnormalities. BAT plays a crucial role in regulating energy expenditure and systemic insulin sensitivity, making it an attractive target for the treatment of obesity and metabolic diseases. Recent research suggests that impaired BAT function and mass may contribute to the link between metabolic disturbances and reproductive issues in PCOS. Additionally, abnormal white adipose tissue (WAT) can exacerbate these conditions by releasing adipokines and nonesterified fatty acids. In this review, we explored the impact of WAT changes on BAT function in PCOS and discussed the potential of BAT activation as a therapeutic strategy to improve PCOS symptoms. We propose that BAT activation holds promise for managing PCOS; however, further research is needed to confirm its efficacy and to develop clinically feasible methods for BAT activation.
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Affiliation(s)
- Khadijeh Abbasi
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Reza Zarezadeh
- Women's Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amir Valizadeh
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amir Mehdizadeh
- Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hamed Hamishehkar
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Nouri
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Masoud Darabi
- Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Division of Experimental Oncology, Department of Hematology and Oncology, University Medical Center Schleswig-Holstein, Campus Lübeck, Germany.
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Mirzababaei A, Mahmoodi M, Keshtkar A, Ashraf H, Abaj F, Soveid N, Hajmir MM, Radmehr M, Khalili P, Mirzaei K. Serum levels of trimethylamine N-oxide and kynurenine novel biomarkers are associated with adult metabolic syndrome and its components: a case-control study from the TEC cohort. Front Nutr 2024; 11:1326782. [PMID: 38321994 PMCID: PMC10844432 DOI: 10.3389/fnut.2024.1326782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Accepted: 01/02/2024] [Indexed: 02/08/2024] Open
Abstract
Background Epidemiologic research suggests that gut microbiota alteration (dysbiosis) may play a role in the pathogenesis of metabolic syndrome (MetS). Dysbiosis can influence Trimethylamine N-oxide (TMAO) a gut microbiota-derived metabolite, as well as kynurenine pathways (KP), which are known as a new marker for an early predictor of chronic diseases. Hence, the current study aimed to investigate the association between KYN and TMAO with MetS and its components. Methods This case-control study was conducted on 250 adults aged 18 years or over of Tehran University of Medical Sciences (TUMS) Employee's Cohort study (TEC) in the baseline phase. Data on the dietary intakes were collected using a validated dish-based food frequency questionnaire (FFQ) and dietary intakes of nitrite and nitrate were estimated using FFQ with 144 items. MetS was defined according to the NCEP ATP criteria. Serum profiles TMAO and KYN were measured by standard protocol. Result The mean level of TMAO and KYN in subjects with MetS was 51.49 pg/mL and 417.56 nmol/l. High levels of TMAO (≥30.39 pg/mL) with MetS were directly correlated, after adjusting for confounding factors, the odds of MetS in individuals 2.37 times increased (OR: 2.37, 95% CI: 1.31-4.28, P-value = 0.004), also, high levels of KYN (≥297.18 nmol/L) increased odds of Mets+ 1.48 times, which is statistically significant (OR: 1.48, 95% CI: 0.83-2.63, P-value = 0.04). High levels of TMAO compared with the reference group increased the odds of hypertriglyceridemia and low HDL in crude and adjusted models (P < 0.05). Additionally, there was a statistically significant high level of KYN increased odds of abdominal obesity (P < 0.05). Conclusion Our study revealed a positive association between serum TMAO and KYN levels and MetS and some of its components. For underlying mechanisms and possible clinical implications of the differences. Prospective studies in healthy individuals are necessary.
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Affiliation(s)
- Atieh Mirzababaei
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Mahmoodi
- Department of Cellular and Molecular Nutrition, School of Nutritional Science and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Abbasali Keshtkar
- Department of Disaster and Emergency Health, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Haleh Ashraf
- Cardiac Primary Prevention Research Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Faezeh Abaj
- Department of Nutrition, Dietetics and Food, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia
| | - Neda Soveid
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahya Mehri Hajmir
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Mina Radmehr
- Department of Nutrition, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Pardis Khalili
- Department of Nutrition, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Khadijeh Mirzaei
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
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Kim JW, Kim JH, Lee YJ. The Role of Adipokines in Tumor Progression and Its Association with Obesity. Biomedicines 2024; 12:97. [PMID: 38255203 PMCID: PMC10813163 DOI: 10.3390/biomedicines12010097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Revised: 12/26/2023] [Accepted: 12/27/2023] [Indexed: 01/24/2024] Open
Abstract
Obesity is a well-established risk factor for various malignancies and emerging evidence suggests that adipokines play a pivotal role in linking excess adiposity to tumorigenesis. Adipokines are bioactive molecules secreted by adipose tissue and their altered expression in obesity contributes to a pro-inflammatory, pro-angiogenic, and growth-promoting microenvironment conducive to tumorigenesis. Leptin, a key adipokine, activates survival and proliferative signaling pathways whereas adiponectin exhibits tumor-suppressive effects by inducing apoptosis and cell cycle arrest. Visfatin has also been documented to promote tumor growth, angiogenesis, migration, and invasion. Moreover, emerging studies suggest that adipokines, such as resistin, apelin, and chemerin, which are overexpressed in obesity, may also possess oncogenic functions. Despite advancements in our understanding of the roles of individual adipokines in cancer, the intricate interplay and crosstalk between adipokines, tumor cells, and the tumor microenvironment remain complex and multifaceted. This review highlights the evolving knowledge of how adipokines contribute to obesity-related tumorigenesis, shedding light on the potential of targeting adipokine signaling pathways as a novel therapeutic approach for obesity-associated cancers. Further research on the specific mechanisms and interactions between adipokines and tumor cells is crucial for a comprehensive understanding of obesity-associated cancer pathogenesis.
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Affiliation(s)
| | | | - Yoon Jae Lee
- Department of Plastic and Reconstructive Surgery, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 07345, Republic of Korea; (J.W.K.); (J.H.K.)
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Mondal S, Basu S, Ghosh S, Guria S, Mukherjee S. Diethyl phthalate, a plasticizer, induces adipocyte inflammation and apoptosis in mice after long-term dietary administration. J Biochem Mol Toxicol 2024; 38:e23561. [PMID: 37942807 DOI: 10.1002/jbt.23561] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Revised: 09/06/2023] [Accepted: 10/02/2023] [Indexed: 11/10/2023]
Abstract
The incidence of metabolic diseases is increasing alarmingly in recent times. Parallel to nutritional excess and sedentary lifestyle, the random usage of several endocrine disrupting chemicals including plasticizers is reported to be closely associated with metabolic diseases. Diethyl phthalate (DEP) is a widely used plasticizer in a host of consumer and daily care products. Adipose tissue plays a central role in energy storage and whole-body metabolism. The impairment of adipose function is critically implicated in the pathogenesis of insulin resistance, diabetes, and related metabolic diseases. Recently, exposure to certain phthalate esters has been linked to the development of obesity and diabetes, although there are contradictions and the mechanisms are not clearly understood. In an effort to ascertain the metabolic consequences of chronic phthalate exposure and the underlying mechanism, the present study was designed to examine the effects of long-term dietary consumption of DEP in adipocytes. DEP-treated mice were hyperglycemic but nonobese; their body weight initially increased which subsequently was reduced compared to control. DEP exposure at lower levels impaired adipogenesis by downregulating the key transcription factor, peroxisome proliferator-activated receptor γ and its downstream insulin-sensitizing adipokine, adiponectin, thereby severely compromising adipocyte function. The activation of master regulator nuclear factor κB led to rise in proinflammatory cytokines. We found that DEP triggered intrinsic apoptotic pathways through activated cytochrome c-Apaf1-caspase 9-caspase 3 axis in adipocytes. Taken together, our data revealed that chronic administration of dietary DEP could unleash adverse metabolic outcomes by initiating oxidative stress, inflammation, and apoptosis in the adipocytes, thus leading to adipose tissue dysfunction.
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Affiliation(s)
- Shirsha Mondal
- Department of Zoology, Endocrinology and Metabolism Laboratory, Visva-Bharati (A Central University), Santiniketan, West Bengal, India
| | - Soumyadeep Basu
- Department of Zoology, Endocrinology and Metabolism Laboratory, Visva-Bharati (A Central University), Santiniketan, West Bengal, India
| | - Songita Ghosh
- Department of Zoology, Endocrinology and Metabolism Laboratory, Visva-Bharati (A Central University), Santiniketan, West Bengal, India
| | - Suktara Guria
- Department of Zoology, Endocrinology and Metabolism Laboratory, Visva-Bharati (A Central University), Santiniketan, West Bengal, India
| | - Sutapa Mukherjee
- Department of Zoology, Endocrinology and Metabolism Laboratory, Visva-Bharati (A Central University), Santiniketan, West Bengal, India
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Tiwari R, Verma S, Verma N, Verma D, Narayan J. Correlation of serum uric acid levels with certain anthropometric parameters in prediabetic and drug-naive diabetic subjects. Ann Afr Med 2024; 23:13-18. [PMID: 38358165 PMCID: PMC10922179 DOI: 10.4103/aam.aam_40_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 05/22/2023] [Accepted: 06/13/2023] [Indexed: 02/16/2024] Open
Abstract
Introduction Uric acid is produced during the metabolism of nucleotide and adenosine triphosphate and contains the final product of human purine metabolism. It acts both as an antioxidant and pro-inflammatory marker and has a positive association with visceral fat in overweight subjects. The aim of the present study is to find an association of uric acid level with certain anthropometric parameters in subjects having type 2 diabetes. Materials and Methods The study included 124 urban drug-naive diabetic Indian subjects above 18 years of age from the general population of the city of North India. Uric acid concentrations were estimated by the uricase method. Fasting plasma glucose (FPG) concentrations were estimated by the glucose oxidase-peroxidase method. Anthropometric measurements and information on lifestyle factors and disease history were collected through in-person meeting. Results All participants of the study subjects had a body mass index (BMI) of more than 23.5. BMI, waist-to-hip ratio (WHR), waist-to-height ratio, waist circumference, neck circumference, weight, age, sagittal abdominal diameter (SAD), skinfold thickness, and body roundness index were positively correlated with the serum uric acid level. The correlation of weight, BMI, SAD, and WHR was statistically significant. Conclusion We found that serum uric acid level increases as body fat content increases. Statistical data show remarkable results for a significant correlation of uric acid level with BMI, WHR, SAD, and FPG. Hypertrophy occurs as a result of inflammatory processes and oxidative stress when the supply of energy starts to exceed the storage capacity of adipocytes, as a result, adipokines such as interleukin (IL)-1, IL-6, and tumor-necrosis factor-alpha are released more frequently which lead to low-grade chronic inflammation. Uric acid levels are much lean toward visceral obesity than overall body fat content.
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Affiliation(s)
- Ritu Tiwari
- Department of Physiology, King George Medical University, Lucknow, Uttar Pradesh, India
| | - Shivam Verma
- Department of Physiology, King George Medical University, Lucknow, Uttar Pradesh, India
| | - Narsingh Verma
- Department of Physiology, King George Medical University, Lucknow, Uttar Pradesh, India
| | - Dileep Verma
- Department of Physiology, King George Medical University, Lucknow, Uttar Pradesh, India
| | - Jagdish Narayan
- Department of Physiology, King George Medical University, Lucknow, Uttar Pradesh, India
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Mir FA, Abdesselem HB, Cyprian F, Iskandarani A, Doudin A, Samra TA, Alkasem M, Abdalhakam I, Taheri S, Abou-Samra AB. Inflammatory protein signatures in individuals with obesity and metabolic syndrome. Sci Rep 2023; 13:22185. [PMID: 38092892 PMCID: PMC10719383 DOI: 10.1038/s41598-023-49643-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 12/10/2023] [Indexed: 12/17/2023] Open
Abstract
There is variability in the metabolic health status among individuals presenting with obesity; some may be metabolically healthy, while others may have developed the metabolic syndrome, a cluster including insulin resistance, hypertension, dyslipidemia, and increased risk of cardiovascular disease and type 2 diabetes. The mechanisms contributing to this metabolic heterogeneity are not fully understood. To address this question, plasma samples from 48 individuals with BMI ≥ 35 kg/m2 were examined (27 with and 21 without metabolic syndrome). Fasting plasma samples were subjected to Olink proteomics analysis for 184 cardiometabolic and inflammation-enriched proteins. Data analysis showed a clear differentiation between the two groups with distinct plasma protein expression profiles. Twenty-four proteins were differentially expressed (DEPs) between the two groups. Pathways related to immune cell migration, leukocyte chemotaxis, chemokine signaling, mucosal inflammatory response, tissue repair and remodeling were enriched in the group with metabolic syndrome. Functional analysis of DEPs revealed upregulation of 15 immunological pathways. The study identifies some of the pathways that are altered and reflect metabolic health in individuals with obesity. This provides valuable insights into some of the underlying mechanisms and can lead to identification of therapeutic targets to improve metabolic health in individuals with obesity.
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Affiliation(s)
- Fayaz Ahmad Mir
- Qatar Metabolic Institute, Academic Health System, Hamad Medical Corporation, PO Box 3050, Doha, Qatar.
| | - Houari B Abdesselem
- Proteomics Core Facility, Office of the Vice President for Research (OVPR), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha, Qatar
- College of Health and Life Sciences (CHLS), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha, Qatar
| | - Farhan Cyprian
- College of Medicine, QU Health, Qatar University, PO Box 2713, Doha, Qatar
| | - Ahmad Iskandarani
- Qatar Metabolic Institute, Academic Health System, Hamad Medical Corporation, PO Box 3050, Doha, Qatar
| | - Asmma Doudin
- Laboratory of Immunoregulation, Research Department, Sidra Medicine, Doha, Qatar
| | - Tareq A Samra
- Qatar Metabolic Institute, Academic Health System, Hamad Medical Corporation, PO Box 3050, Doha, Qatar
| | - Meis Alkasem
- Qatar Metabolic Institute, Academic Health System, Hamad Medical Corporation, PO Box 3050, Doha, Qatar
| | - Ibrahem Abdalhakam
- Qatar Metabolic Institute, Academic Health System, Hamad Medical Corporation, PO Box 3050, Doha, Qatar
| | - Shahrad Taheri
- Qatar Metabolic Institute, Academic Health System, Hamad Medical Corporation, PO Box 3050, Doha, Qatar
- National Obesity Treatment Center, Hamad Medical Corporation, Doha, Qatar
- Weil Cornell Medicine -Qatar, Doha, Qatar
| | - Abdul-Badi Abou-Samra
- Qatar Metabolic Institute, Academic Health System, Hamad Medical Corporation, PO Box 3050, Doha, Qatar
- National Obesity Treatment Center, Hamad Medical Corporation, Doha, Qatar
- Weil Cornell Medicine -Qatar, Doha, Qatar
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Hao Y, Li S, Dong S, Niu L. The Association between Tooth Loss and Insulin Resistance Mediated by Diet Quality and Systemic Immunoinflammatory Index. Nutrients 2023; 15:5008. [PMID: 38068866 PMCID: PMC10708050 DOI: 10.3390/nu15235008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 11/28/2023] [Accepted: 11/30/2023] [Indexed: 12/18/2023] Open
Abstract
(1) Background: Both tooth loss and diabetes have high global prevalence, and both have a significant influence on patients' general health and quality of life. Previous research has indicated a possible connection between tooth loss and diabetes, but it has been unclear whether tooth loss has an effect on the development of diabetes and how it affects it. We aim to investigate the relationship between insulin resistance (IR) and tooth loss and examine how the systemic immune-inflammation index (SII) level and diet quality mediate it. (2) Methods: The cross-sectional study data were obtained from the National Health and Nutrition Examination Survey (NHANES). After describing and comparing baseline data, we used regression models to evaluate the relationship between IR and tooth loss, diet quality and tooth loss and IR, SII and tooth loss and IR. Furthermore, we applied bootstrapping to test the mediation effect of diet quality and SII between tooth loss and IR. Diet quality is reflected by the HEI (Healthy Eating Index)-2015 score. (3) Results: The total number of subjects included was 8197, with 3861 individuals belonging to the IR group (HOMA-IR ≥ 2.5) and 4336 in the non-IR group (HOMA-IR < 2.5). In the model with all covariates adjusted, tooth loss in the fourth quartile was found to be positively correlated with an increase in HOMA-IR (OR = 1.301; 95% confidence interval (CI) = [1.102, 1.537]; p < 0.001) compared to the first quartile; tooth loss in the fourth quartile correlated with the HEI-2015 score compared to the first quantile (β = -0.121, 95% CI = [-4.839, -2.974], p < 0.001); and the highest number of tooth loss was found to have a significant effect on SII (β = 0.032; 95%CI = [1.777, 47.448]; p < 0.05). Compared to average diet quality, best diet quality acts as a safeguard against elevated HOMA-IR (OR = 0.776; 95% CI = [0.641, 0.939]; p < 0.01); inadequate diet quality is a risk factor (OR = 1.267; 95%CI = [1.138, 1.411]; p < 0.001) conversely. Meanwhile, it can be seen that compared with the first quantile of SII, the highest score is significantly correlated with the higher incidence of IR (OR = 1.363; 95%CI = [1.179, 1.575]; p < 0.001). Diet quality and SII played a partial mediating role in the relationship between HOMA-IR and tooth loss, and the mediating effect ratio for the total effect value was 4.731% and 4.576%, respectively. The mediating effect of SII and diet quality in the association of the relationship between HOMA-IR and tooth loss both was 0.003 (95%CI = [0.001, 0.004]). (4) Conclusions: Our study revealed the relationship between IR and tooth loss, and further explored the mediating role of SII and diet quality between the number of missing teeth and IR, emphasizing that improving diet quality and reducing SII can effectively prevent and treat IR and related diseases. It provides new theoretical support for the study of IR mechanisms and new ideas and approaches to deal with related diseases.
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Affiliation(s)
- Yaqi Hao
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi’an Jiaotong University, Xi’an 710004, China; (Y.H.); (S.D.)
- Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, Xi’an 710004, China
| | - Shaoru Li
- Experimental Teaching Center, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China;
| | - Shaojie Dong
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi’an Jiaotong University, Xi’an 710004, China; (Y.H.); (S.D.)
- Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, Xi’an 710004, China
- Department of Prosthodontics, College of Stomatology, Xi’an Jiaotong University, Xi’an 710004, China
| | - Lin Niu
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi’an Jiaotong University, Xi’an 710004, China; (Y.H.); (S.D.)
- Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, Xi’an 710004, China
- Department of Prosthodontics, College of Stomatology, Xi’an Jiaotong University, Xi’an 710004, China
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Ting R, Dutton H, Sorisky A. In vitro studies of the renin-angiotensin system in human adipose tissue/adipocytes and possible relationship to SARS-CoV-2: a scoping review. Adipocyte 2023; 12:2194034. [PMID: 36973648 PMCID: PMC10054178 DOI: 10.1080/21623945.2023.2194034] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 01/02/2023] [Indexed: 03/29/2023] Open
Abstract
The renin-angiotensin system (RAS) operates within adipose tissue. Obesity-related changes can affect adipose RAS, predisposing to hypertension, type 2 diabetes, and possibly severe COVID-19. We evaluated the in vitro research on human adipose RAS and identified gaps in the literature. Medline (Ovid), Embase (Ovid), Web of Science, Scopus, and 1findr were searched to identify relevant studies. Fifty primary studies met our inclusion criteria for analysis. Expression of RAS components (n = 14), role in differentiation (n = 14), association with inflammation (n = 15) or blood pressure (n = 7) were investigated. We found (1) obesity-related changes in RAS were frequently studied (30%); (2) an upswing of articles investigating adipose ACE-2 expression since the COVID-19 pandemic; (3) a paucity of papers on AT2R and Ang (1-7)/MasR which counterbalance Ang II/ART1; (4) weight loss lowered adipose ACE-2 mRNA expression; and (5) angiotensin receptor blockers (ARBs) reduced deleterious effects of angiotensin II. Overall, these studies link Ang II/ATR1 signalling to impaired adipogenesis and a pro-inflammatory dysfunctional adipose tissue, with ATR1 blockade limiting these responses. ACE-2 may mitigate Ang II effects by converting it to Ang(1-7) which binds MasR. More work is needed to understand adipose RAS in various pathologic states such as obesity and COVID-19 infection.T.
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Affiliation(s)
- Ryan Ting
- Faculty of Medicine, University of Ottawa, Ottawa, Canada
| | - Heidi Dutton
- Faculty of Medicine, University of Ottawa, Ottawa, Canada
- Department of Medicine, University of Ottawa, Ottawa, Canada
- The Ottawa Hospital/Ottawa Hospital Research Institute, Ottawa, Canada
| | - Alexander Sorisky
- Faculty of Medicine, University of Ottawa, Ottawa, Canada
- Department of Medicine, University of Ottawa, Ottawa, Canada
- The Ottawa Hospital/Ottawa Hospital Research Institute, Ottawa, Canada
- Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Canada
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Khocht A, Paster B, Lenoir L, Irani C, Fraser G. Metabolomic profiles of obesity and subgingival microbiome in periodontally healthy individuals: A cross-sectional study. J Clin Periodontol 2023; 50:1455-1466. [PMID: 37536958 DOI: 10.1111/jcpe.13860] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 07/19/2023] [Accepted: 07/22/2023] [Indexed: 08/05/2023]
Abstract
AIM Since blood metabolomic profiles of obese individuals are known to be altered, our objective was to examine the association between obesity-related metabolic patterns and subgingival microbial compositions in obese and non-obese periodontally healthy individuals. MATERIALS AND METHODS Thirty-nine periodontally healthy subjects were enrolled. Based on body mass index scores, 20 subjects were categorized as lean and 19 as obese. A comprehensive periodontal examination was performed. Subgingival plaque and blood samples were collected. Plaque samples were analysed for bacteria using 16S rDNA sequencing. Untargeted metabolomic profiling (mass spectrometry) was used to quantify metabolites in serum. RESULTS Obese subjects were statistically associated with several periodontopathic taxa including Dialister invisus, Prevotella intermedia, Prevotella denticola, Fusobacterium nucleatum_subsp.vincentii, Mogibacterium diversum, Parvimonas micra and Shuttleworthia satelles. In obese individuals, an amino acid-related metabolic pattern was elevated; however, there was a decrease in metabolic patterns related to lipids and cofactor/vitamins. These metabolic perturbations were associated with multiple subgingival bacterial species that differentiated lean from obese individuals. CONCLUSIONS Obesity-related perturbations in circulating blood metabolites are associated with the development of periodontopathic bacterial colonization in the subgingival microbiome and consequently may increase the risk for periodontal disease in obese individuals.
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Affiliation(s)
- Ahmed Khocht
- Department of Periodontics, School of Dentistry, Loma Linda University, Loma Linda, California, USA
| | - Bruce Paster
- Department of Molecular Genetics, Forsyth Institute, Cambridge, Massachusetts, USA
| | - Leticia Lenoir
- Department of Periodontics, School of Dentistry, Loma Linda University, Loma Linda, California, USA
| | - Crissy Irani
- Institute for Community Partnerships, Loma Linda University Health, Loma Linda, California, USA
| | - Gary Fraser
- Department of Preventive Medicine, School of Medicine, Loma Linda University, Loma Linda, California, USA
- School of Public Health, Loma Linda University, Loma Linda, California, USA
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Ruenkham A, Uitrakul S, Oberdorfer P, Okonogi S, Katip W. Comparative Safety and Effectiveness of Heterologous CoronaVac-ChAdOx1 versus Homologous CoronaVac Vaccination in a Real-World Setting: A Retrospective Cohort Study. Vaccines (Basel) 2023; 11:1458. [PMID: 37766134 PMCID: PMC10535109 DOI: 10.3390/vaccines11091458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Revised: 08/31/2023] [Accepted: 09/02/2023] [Indexed: 09/29/2023] Open
Abstract
Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has outpaced vaccine availability and delivery from vaccine manufacturers, and thus, a scarcity of vaccines happened to many countries around the world. In Thailand, the mixing of different types of vaccines was approved and clinically implemented partially due to concerns about the availability and efficacy of one vaccine. Objective: This study aimed to investigate the effectiveness and safety of heterologous CoronaVac-ChAdOx1 nCoV-19 vaccines compared with the usual regimen of homologous CoronaVac-CoronaVac. A retrospective cohort study was conducted by dividing patients into the CoronaVac-CoronaVac group and the CoronaVac-ChAdOx1 group. Results: A total of 875 patients received vaccinations at Srisangwan Hospital between April to October 2021 and were included for analysis. The patients in both homologous and heterologous groups had low rates of COVID-19 infection. In addition, the hospitalization rates in the 40 days after the second vaccination were low in both regimens. Minimal adverse events (AE) were reported in both groups, including local AE (e.g., discomfort at the injection site, rash, soreness, swelling, and redness) and systemic AE (e.g., fever, headache, weariness, nausea, vomiting, diarrhoea, and myalgia). Moreover, several factors were associated with lower adverse events following immunization (AEFIs), including age ≥ 50 years, male, and body weight ≥ 50 kg. In contrast, thyroid disease, diabetes mellitus, allergic rhinitis, and psychiatric disorders were independent risk factors associated with an increase in AEFIs. Conclusions: The heterologous CoronaVac-ChAdOx1 and homologous CoronaVac-CoronaVac regimens were promising vaccination strategies for the prevention of SARS-CoV-2 infection. However, the heterologous CoronaVac-ChAdOx1 potentially caused fewer AEFIs compared with the homologous CoronaVac-CoronaVac regimen.
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Affiliation(s)
- Ayakarn Ruenkham
- Department of Pharmacy, Srisangwan Hospital, Mae Hong Son 58000, Thailand
| | - Suriyon Uitrakul
- Department of Pharmaceutical Care, School of Pharmacy, Walailak University, Nakhon Si Thammarat 80160, Thailand;
| | - Peninnah Oberdorfer
- Epidemiology Research Group of Infectious Disease (ERGID), Chiang Mai University, Chiang Mai 50200, Thailand;
- Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Siriporn Okonogi
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand;
- Center of Excellence in Pharmaceutical Nanotechnology, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Wasan Katip
- Epidemiology Research Group of Infectious Disease (ERGID), Chiang Mai University, Chiang Mai 50200, Thailand;
- Center of Excellence in Pharmaceutical Nanotechnology, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand
- Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand
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Zheng HY, Wang YX, Zhou K, Xie HL, Ren Z, Liu HT, Ou YS, Zhou ZX, Jiang ZS. Biological functions of CRTC2 and its role in metabolism-related diseases. J Cell Commun Signal 2023; 17:495-506. [PMID: 36856929 PMCID: PMC10409973 DOI: 10.1007/s12079-023-00730-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 02/01/2023] [Indexed: 03/02/2023] Open
Abstract
CREB-regulated transcription coactivator2 (CRTC2 or TORC2) is a transcriptional coactivator of CREB(cAMP response element binding protein), which affects human energy metabolism through cyclic adenosine phosphate pathway, Mammalian target of rapamycin (mTOR) pathway, Sterol regulatory element binding protein 1(SREBP1), Sterol regulatory element binding protein 2 (SREBP2) and other substances Current studies on CRTC2 mainly focus on glucose and lipid metabolism, relevant studies show that CRTC2 can participate in the occurrence and development of related diseases by affecting metabolic homeostasis. It has been found that Crtc2 acts as a signaling regulator for cAMP and Ca2 + signaling pathways in many cell types, and phosphorylation at ser171 and ser275 can regulate downstream biological functions by controlling CRTC2 shuttling between cytoplasm and nucleus.
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Affiliation(s)
- Hong-Yu Zheng
- Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, International Joint Laboratory for Arteriosclerotic Disease Research of Hunan Province, University of South China, Hengyang, 421001, China
| | - Yan-Xia Wang
- Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, International Joint Laboratory for Arteriosclerotic Disease Research of Hunan Province, University of South China, Hengyang, 421001, China
| | - Kun Zhou
- Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, International Joint Laboratory for Arteriosclerotic Disease Research of Hunan Province, University of South China, Hengyang, 421001, China
| | - Hai-Lin Xie
- Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, International Joint Laboratory for Arteriosclerotic Disease Research of Hunan Province, University of South China, Hengyang, 421001, China
| | - Zhong Ren
- Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, International Joint Laboratory for Arteriosclerotic Disease Research of Hunan Province, University of South China, Hengyang, 421001, China
| | - Hui-Ting Liu
- Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, International Joint Laboratory for Arteriosclerotic Disease Research of Hunan Province, University of South China, Hengyang, 421001, China
| | - Yang-Shao Ou
- Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, International Joint Laboratory for Arteriosclerotic Disease Research of Hunan Province, University of South China, Hengyang, 421001, China
| | - Zhi-Xiang Zhou
- Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, International Joint Laboratory for Arteriosclerotic Disease Research of Hunan Province, University of South China, Hengyang, 421001, China
| | - Zhi-Sheng Jiang
- Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, International Joint Laboratory for Arteriosclerotic Disease Research of Hunan Province, University of South China, Hengyang, 421001, China.
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Bielczyk-Maczynska E, Sharma D, Blencowe M, Saliba Gustafsson P, Gloudemans MJ, Yang X, Carcamo-Orive I, Wabitsch M, Svensson KJ, Park CY, Quertermous T, Knowles JW, Li J. A single-cell CRISPRi platform for characterizing candidate genes relevant to metabolic disorders in human adipocytes. Am J Physiol Cell Physiol 2023; 325:C648-C660. [PMID: 37486064 PMCID: PMC10635647 DOI: 10.1152/ajpcell.00148.2023] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 07/07/2023] [Accepted: 07/19/2023] [Indexed: 07/25/2023]
Abstract
CROP-Seq combines gene silencing using CRISPR interference with single-cell RNA sequencing. Here, we applied CROP-Seq to study adipogenesis and adipocyte biology. Human preadipocyte SGBS cell line expressing KRAB-dCas9 was transduced with a sgRNA library. Following selection, individual cells were captured using microfluidics at different timepoints during adipogenesis. Bioinformatic analysis of transcriptomic data was used to determine the knockdown effects, the dysregulated pathways, and to predict cellular phenotypes. Single-cell transcriptomes recapitulated adipogenesis states. For all targets, over 400 differentially expressed genes were identified at least at one timepoint. As a validation of our approach, the knockdown of PPARG and CEBPB (which encode key proadipogenic transcription factors) resulted in the inhibition of adipogenesis. Gene set enrichment analysis generated hypotheses regarding the molecular function of novel genes. MAFF knockdown led to downregulation of transcriptional response to proinflammatory cytokine TNF-α in preadipocytes and to decreased CXCL-16 and IL-6 secretion. TIPARP knockdown resulted in increased expression of adipogenesis markers. In summary, this powerful, hypothesis-free tool can identify novel regulators of adipogenesis, preadipocyte, and adipocyte function associated with metabolic disease.NEW & NOTEWORTHY Genomics efforts led to the identification of many genomic loci that are associated with metabolic traits, many of which are tied to adipose tissue function. However, determination of the causal genes, and their mechanism of action in metabolism, is a time-consuming process. Here, we use an approach to determine the transcriptional outcome of candidate gene knockdown for multiple genes at the same time in a human cell model of adipogenesis.
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Affiliation(s)
- Ewa Bielczyk-Maczynska
- Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, United States
- Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, California, United States
- Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, United States
| | - Disha Sharma
- Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, United States
- Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, United States
| | - Montgomery Blencowe
- Department of Integrative Biology and Physiology, University of California, Los Angeles, California, United States
| | - Peter Saliba Gustafsson
- Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, United States
- Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, California, United States
- Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, United States
- Cardiovascular Medicine Unit, Department of Medicine, Center for Molecular Medicine at BioClinicum, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
| | - Michael J Gloudemans
- Department of Pathology, Stanford University School of Medicine, Stanford, California, United States
- Biomedical Informatics Training Program, Stanford, California, United States
| | - Xia Yang
- Department of Integrative Biology and Physiology, University of California, Los Angeles, California, United States
| | - Ivan Carcamo-Orive
- Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, United States
- Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, California, United States
- Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, United States
| | - Martin Wabitsch
- Department of Pediatrics and Adolescent Medicine, Center for Rare Endocrine Diseases, Division of Pediatric Endocrinology and Diabetes, Ulm University Medical Centre, Ulm, Germany
| | - Katrin J Svensson
- Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, California, United States
- Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, United States
- Department of Pathology, Stanford University School of Medicine, Stanford, California, United States
| | - Chong Y Park
- Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, United States
- Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, United States
| | - Thomas Quertermous
- Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, United States
- Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, United States
| | - Joshua W Knowles
- Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, United States
- Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, California, United States
- Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, United States
- Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, California, United States
| | - Jiehan Li
- Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, United States
- Stanford Diabetes Research Center, Stanford University School of Medicine, Stanford, California, United States
- Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, United States
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Horwitz A, Birk R. Adipose Tissue Hyperplasia and Hypertrophy in Common and Syndromic Obesity-The Case of BBS Obesity. Nutrients 2023; 15:3445. [PMID: 37571382 PMCID: PMC10421039 DOI: 10.3390/nu15153445] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 07/16/2023] [Accepted: 07/31/2023] [Indexed: 08/13/2023] Open
Abstract
Obesity is a metabolic state generated by the expansion of adipose tissue. Adipose tissue expansion depends on the interplay between hyperplasia and hypertrophy, and is mainly regulated by a complex interaction between genetics and excess energy intake. However, the genetic regulation of adipose tissue expansion is yet to be fully understood. Obesity can be divided into common multifactorial/polygenic obesity and monogenic obesity, non-syndromic and syndromic. Several genes related to obesity were found through studies of monogenic non-syndromic obesity models. However, syndromic obesity, characterized by additional features other than obesity, suggesting a more global role of the mutant genes related to the syndrome and, thus, an additional peripheral influence on the development of obesity, were hardly studied to date in this regard. This review summarizes present knowledge regarding the hyperplasia and hypertrophy of adipocytes in common obesity. Additionally, we highlight the scarce research on syndromic obesity as a model for studying adipocyte hyperplasia and hypertrophy, focusing on Bardet-Biedl syndrome (BBS). BBS obesity involves central and peripheral mechanisms, with molecular and mechanistic alternation in adipocyte hyperplasia and hypertrophy. Thus, we argue that using syndromic obesity models, such as BBS, can further advance our knowledge regarding peripheral adipocyte regulation in obesity.
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Affiliation(s)
| | - Ruth Birk
- Department of Nutrition, Faculty of Health Sciences, Ariel University, Ariel 40700, Israel;
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Siegel-Axel D, Barroso Oquendo M, Gerst F, Fend F, Wagner R, Heni M, Königsrainer A, Häring HU, Fritsche A, Schleicher E, Birkenfeld AL, Stefan N. Extracellular Matrix Expression in Human Pancreatic Fat Cells of Patients with Normal Glucose Regulation, Prediabetes and Type 2 Diabetes. Int J Mol Sci 2023; 24:11169. [PMID: 37446346 DOI: 10.3390/ijms241311169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 06/28/2023] [Accepted: 06/28/2023] [Indexed: 07/15/2023] Open
Abstract
Previously, we found that human pancreatic preadipocytes (PPAs) and islets influence each other and that the crosstalk with the fatty liver via the hepatokine fetuin-A/palmitate induces inflammatory responses. Here, we examined whether the mRNA-expression of pancreatic extracellular matrix (ECM)-forming and -degrading components differ in PPAs from individuals with normal glucose regulation (PPAs-NGR), prediabetes (PPAs-PD), and type 2 diabetes (PPAs-T2D), and whether fetuin-A/palmitate impacts ECM-formation/degradation and associated monocyte invasion. Human pancreatic resections were analyzed (immuno)histologically. PPAs were studied for mRNA expression by real-time PCR and protein secretion by Luminex analysis. Furthermore, co-cultures with human islets and monocyte migration assays in Transwell plates were conducted. We found that in comparison with NGR-PPAs, TIMP-2 mRNA levels were lower in PPAs-PD, and TGF-β1 mRNA levels were higher in PPAs-T2D. Fetuin-A/palmitate reduced fibronectin, decorin, TIMP-1/-2 and TGF-ß1 mRNA levels. Only fibronectin was strongly downregulated by fetuin-A/palmitate independently of the glycemic status. Co-culturing of PPAs with islets increased TIMP-1 mRNA expression in islets. Fetuin-A/palmitate increased MMP-1, usherin and dermatopontin mRNA-levels in co-cultured islets. A transmigration assay showed increased monocyte migration towards PPAs, which was enhanced by fetuin-A/palmitate. This was more pronounced in PPAs-T2D. The expression of distinct ECM components differs in PPAs-PD and PPAs-T2D compared to PPAs-NGR, suggesting that ECM alterations can occur even in mild hyperglycemia. Fetuin-A/palmitate impacts on ECM formation/degradation in PPAs and co-cultured islets. Fetuin-A/palmitate also enhances monocyte migration, a process which might impact on matrix turnover.
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Affiliation(s)
- Dorothea Siegel-Axel
- Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, 72076 Tübingen, Germany
- German Center for Diabetes Research (DZD e.V.), 85764 Neuherberg, Germany
- Department of Internal Medicine IV, University Hospital of Tübingen, Otfried-Müller Str. 10, 72076 Tübingen, Germany
| | - Morgana Barroso Oquendo
- Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, 72076 Tübingen, Germany
- German Center for Diabetes Research (DZD e.V.), 85764 Neuherberg, Germany
- Department of Internal Medicine IV, University Hospital of Tübingen, Otfried-Müller Str. 10, 72076 Tübingen, Germany
- EKU Tübingen, Quantitative Biology Center (QBiC), University of Tübingen, 72076 Tübingen, Germany
| | - Felicia Gerst
- Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, 72076 Tübingen, Germany
- German Center for Diabetes Research (DZD e.V.), 85764 Neuherberg, Germany
- Department of Internal Medicine IV, University Hospital of Tübingen, Otfried-Müller Str. 10, 72076 Tübingen, Germany
| | - Falko Fend
- Department of General Pathology and Pathological Anatomy, University Hospital Tübingen, 72076 Tübingen, Germany
| | - Robert Wagner
- Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, 72076 Tübingen, Germany
- German Center for Diabetes Research (DZD e.V.), 85764 Neuherberg, Germany
- Department of Internal Medicine IV, University Hospital of Tübingen, Otfried-Müller Str. 10, 72076 Tübingen, Germany
- Institute for Clinical Diabetology, German Diabetes Center (DDZ), Heinrich Heine University Düsseldorf (HHU), 40225 Düsseldorf, Germany
| | - Martin Heni
- Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, 72076 Tübingen, Germany
- German Center for Diabetes Research (DZD e.V.), 85764 Neuherberg, Germany
- Department of Internal Medicine IV, University Hospital of Tübingen, Otfried-Müller Str. 10, 72076 Tübingen, Germany
- Division of Endocrinology and Diabetology, Department of Internal Medicine I, University Hospital Ulm, 89081 Ulm, Germany
| | - Alfred Königsrainer
- Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, 72076 Tübingen, Germany
| | - Hans-Ulrich Häring
- Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, 72076 Tübingen, Germany
- German Center for Diabetes Research (DZD e.V.), 85764 Neuherberg, Germany
- Department of Internal Medicine IV, University Hospital of Tübingen, Otfried-Müller Str. 10, 72076 Tübingen, Germany
| | - Andreas Fritsche
- Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, 72076 Tübingen, Germany
- German Center for Diabetes Research (DZD e.V.), 85764 Neuherberg, Germany
- Department of Internal Medicine IV, University Hospital of Tübingen, Otfried-Müller Str. 10, 72076 Tübingen, Germany
| | - Erwin Schleicher
- Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, 72076 Tübingen, Germany
- German Center for Diabetes Research (DZD e.V.), 85764 Neuherberg, Germany
- Department of Internal Medicine IV, University Hospital of Tübingen, Otfried-Müller Str. 10, 72076 Tübingen, Germany
- Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital Tübingen, 72076 Tübingen, Germany
| | - Andreas L Birkenfeld
- Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, 72076 Tübingen, Germany
- German Center for Diabetes Research (DZD e.V.), 85764 Neuherberg, Germany
- Department of Internal Medicine IV, University Hospital of Tübingen, Otfried-Müller Str. 10, 72076 Tübingen, Germany
| | - Norbert Stefan
- Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, 72076 Tübingen, Germany
- German Center for Diabetes Research (DZD e.V.), 85764 Neuherberg, Germany
- Department of Internal Medicine IV, University Hospital of Tübingen, Otfried-Müller Str. 10, 72076 Tübingen, Germany
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46
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Xu ZH, Xiong CW, Miao KS, Yu ZT, Zhang JJ, Yu CL, Huang Y, Zhou XD. Adipokines regulate mesenchymal stem cell osteogenic differentiation. World J Stem Cells 2023; 15:502-513. [PMID: 37424950 PMCID: PMC10324509 DOI: 10.4252/wjsc.v15.i6.502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 02/26/2023] [Accepted: 04/24/2023] [Indexed: 06/26/2023] Open
Abstract
Mesenchymal stem cells (MSCs) can differentiate into various tissue cell types including bone, adipose, cartilage, and muscle. Among those, osteogenic differentiation of MSCs has been widely explored in many bone tissue engineering studies. Moreover, the conditions and methods of inducing osteogenic differentiation of MSCs are continuously advancing. Recently, with the gradual recognition of adipokines, the research on their involvement in different pathophysiological processes of the body is also deepening including lipid metabolism, inflammation, immune regulation, energy disorders, and bone homeostasis. At the same time, the role of adipokines in the osteogenic differentiation of MSCs has been gradually described more completely. Therefore, this paper reviewed the evidence of the role of adipokines in the osteogenic differentiation of MSCs, emphasizing bone formation and bone regeneration.
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Affiliation(s)
- Zhong-Hua Xu
- Department of Orthopedics, Jintan Hospital Affiliated to Jiangsu University, Changzhou 213200, Jiangsu Province, China
| | - Chen-Wei Xiong
- Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
- Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
| | - Kai-Song Miao
- Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
- Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
| | - Zhen-Tang Yu
- Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
- Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
| | - Jun-Jie Zhang
- Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
- Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
| | - Chang-Lin Yu
- Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
- Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
| | - Yong Huang
- Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
- Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
| | - Xin-Die Zhou
- Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
- Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
- Department of Orthopedics, Gonghe County Hospital of Traditional Chinese Medicine, Hainan Tibetan Autonomous Prefecture 811800, Qinghai Province, China
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47
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Liu FS, Wang S, Guo XS, Ye ZX, Zhang HY, Li Z. State of art on the mechanisms of laparoscopic sleeve gastrectomy in treating type 2 diabetes mellitus. World J Diabetes 2023; 14:632-655. [PMID: 37383590 PMCID: PMC10294061 DOI: 10.4239/wjd.v14.i6.632] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Revised: 04/01/2023] [Accepted: 04/24/2023] [Indexed: 06/14/2023] Open
Abstract
Obesity and type-2 diabetes mellitus (T2DM) are metabolic disorders. Obesity increases the risk of T2DM, and as obesity is becoming increasingly common, more individuals suffer from T2DM, which poses a considerable burden on health systems. Traditionally, pharmaceutical therapy together with lifestyle changes is used to treat obesity and T2DM to decrease the incidence of comorbidities and all-cause mortality and to increase life expectancy. Bariatric surgery is increasingly replacing other forms of treatment of morbid obesity, especially in patients with refractory obesity, owing to its many benefits including good long-term outcomes and almost no weight regain. The bariatric surgery options have markedly changed recently, and laparoscopic sleeve gastrectomy (LSG) is gradually gaining popularity. LSG has become an effective and safe treatment for type-2 diabetes and morbid obesity, with a high cost-benefit ratio. Here, we review the me-chanism associated with LSG treatment of T2DM, and we discuss clinical studies and animal experiments with regard to gastrointestinal hormones, gut microbiota, bile acids, and adipokines to clarify current treatment modalities for patients with obesity and T2DM.
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Affiliation(s)
- Fa-Shun Liu
- Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China
| | - Song Wang
- Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China
| | - Xian-Shan Guo
- Department of Endocrinology, Xinxiang Central Hospital, Xinxiang 453000, Henan Province, China
| | - Zhen-Xiong Ye
- Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China
| | - Hong-Ya Zhang
- Central Laboratory, Yangpu District Control and Prevention Center, Shanghai 200090, China
| | - Zhen Li
- Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China
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48
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Rivera-Gonzalez GC, Butka EG, Gonzalez CE, Kong W, Jindal K, Morris SA. Single-cell lineage tracing reveals hierarchy and mechanism of adipocyte precursor maturation. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.06.01.543318. [PMID: 37398135 PMCID: PMC10312565 DOI: 10.1101/2023.06.01.543318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/04/2023]
Abstract
White adipose tissue is crucial in various physiological processes. In response to high caloric intake, adipose tissue may expand by generating new adipocytes. Adipocyte precursor cells (progenitors and preadipocytes) are essential for generating mature adipocytes, and single-cell RNA sequencing provides new means to identify these populations. Here, we characterized adipocyte precursor populations in the skin, an adipose depot with rapid and robust generation of mature adipocytes. We identified a new population of immature preadipocytes, revealed a biased differentiation potential of progenitor cells, and identified Sox9 as a critical factor in driving progenitors toward adipose commitment, the first known mechanism of progenitor differentiation. These findings shed light on the specific dynamics and molecular mechanisms underlying rapid adipogenesis in the skin.
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Affiliation(s)
- Guillermo C. Rivera-Gonzalez
- Department of Developmental Biology, Washington University School of Medicine; 660 S. Euclid Avenue, St. Louis, MO 63110, USA
- Department of Genetics, Washington University School of Medicine; 660 S. Euclid Avenue, St. Louis, MO 63110, USA
- Center of Regenerative Medicine, Washington University School of Medicine; 660 S. Euclid Avenue, St. Louis, MO 63110, USA
| | - Emily G. Butka
- Department of Developmental Biology, Washington University School of Medicine; 660 S. Euclid Avenue, St. Louis, MO 63110, USA
- Department of Genetics, Washington University School of Medicine; 660 S. Euclid Avenue, St. Louis, MO 63110, USA
- Center of Regenerative Medicine, Washington University School of Medicine; 660 S. Euclid Avenue, St. Louis, MO 63110, USA
| | - Carolynn E. Gonzalez
- Department of Developmental Biology, Washington University School of Medicine; 660 S. Euclid Avenue, St. Louis, MO 63110, USA
- Department of Genetics, Washington University School of Medicine; 660 S. Euclid Avenue, St. Louis, MO 63110, USA
- Center of Regenerative Medicine, Washington University School of Medicine; 660 S. Euclid Avenue, St. Louis, MO 63110, USA
| | - Wenjun Kong
- Department of Developmental Biology, Washington University School of Medicine; 660 S. Euclid Avenue, St. Louis, MO 63110, USA
- Department of Genetics, Washington University School of Medicine; 660 S. Euclid Avenue, St. Louis, MO 63110, USA
- Center of Regenerative Medicine, Washington University School of Medicine; 660 S. Euclid Avenue, St. Louis, MO 63110, USA
| | - Kunal Jindal
- Department of Developmental Biology, Washington University School of Medicine; 660 S. Euclid Avenue, St. Louis, MO 63110, USA
- Department of Genetics, Washington University School of Medicine; 660 S. Euclid Avenue, St. Louis, MO 63110, USA
- Center of Regenerative Medicine, Washington University School of Medicine; 660 S. Euclid Avenue, St. Louis, MO 63110, USA
| | - Samantha A. Morris
- Department of Developmental Biology, Washington University School of Medicine; 660 S. Euclid Avenue, St. Louis, MO 63110, USA
- Department of Genetics, Washington University School of Medicine; 660 S. Euclid Avenue, St. Louis, MO 63110, USA
- Center of Regenerative Medicine, Washington University School of Medicine; 660 S. Euclid Avenue, St. Louis, MO 63110, USA
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Abstract
The circadian clock plays an essential role in coordinating feeding and metabolic rhythms with the light/dark cycle. Disruption of clocks is associated with increased adiposity and metabolic disorders, whereas aligning feeding time with cell-autonomous rhythms in metabolism improves health. Here, we provide a comprehensive overview of recent literature in adipose tissue biology as well as our understanding of molecular mechanisms underlying the circadian regulation of transcription, metabolism, and inflammation in adipose tissue. We highlight recent efforts to uncover the mechanistic links between clocks and adipocyte metabolism, as well as its application to dietary and behavioral interventions to improve health and mitigate obesity.
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Affiliation(s)
- Chelsea Hepler
- Department of Medicine, Division of Endocrinology, Metabolism, and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
| | - Joseph Bass
- Department of Medicine, Division of Endocrinology, Metabolism, and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
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50
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Nainu F, Frediansyah A, Mamada SS, Permana AD, Salampe M, Chandran D, Emran TB, Simal-Gandara J. Natural products targeting inflammation-related metabolic disorders: A comprehensive review. Heliyon 2023; 9:e16919. [PMID: 37346355 PMCID: PMC10279840 DOI: 10.1016/j.heliyon.2023.e16919] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Revised: 05/31/2023] [Accepted: 06/01/2023] [Indexed: 06/23/2023] Open
Abstract
Currently, the incidence of metabolic disorders is increasing, setting a challenge to global health. With major advancement in the diagnostic tools and clinical procedures, much has been known in the etiology of metabolic disorders and their corresponding pathophysiologies. In addition, the use of in vitro and in vivo experimental models prior to clinical studies has promoted numerous biomedical breakthroughs, including in the discovery and development of drug candidates to treat metabolic disorders. Indeed, chemicals isolated from natural products have been extensively studied as prospective drug candidates to manage diabetes, obesity, heart-related diseases, and cancer, partly due to their antioxidant and anti-inflammatory properties. Continuous efforts have been made in parallel to improve their bioactivity and bioavailability using selected drug delivery approaches. Here, we provide insights on recent progress in the role of inflammatory-mediated responses on the initiation of metabolic disorders, with particular reference to diabetes mellitus, obesity, heart-related diseases, and cancer. In addition, we discussed the prospective role of natural products in the management of diabetes, obesity, heart-related diseases, and cancers and provide lists of potential biological targets for high throughput screening in drug discovery and development. Lastly, we discussed findings observed in the preclinical and clinical studies prior to identifying suitable approaches on the phytochemical drug delivery systems that are potential to be used in the treatment of metabolic disorders.
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Affiliation(s)
- Firzan Nainu
- Department of Pharmacy, Faculty of Pharmacy, Hasanuddin University, Tamalanrea, Makassar 90245, Indonesia
| | - Andri Frediansyah
- Research Center for Food Technology and Processing (PRTPP), National Research and Innovation Agency (BRIN), Yogyakarta 55861, Indonesia
| | - Sukamto S. Mamada
- Department of Pharmacy, Faculty of Pharmacy, Hasanuddin University, Tamalanrea, Makassar 90245, Indonesia
| | - Andi Dian Permana
- Department of Pharmaceutical Science and Technology, Faculty of Pharmacy, Hasanuddin University, Tamalanrea, Makassar 90245, Indonesia
| | | | - Deepak Chandran
- Department of Veterinary Sciences and Animal Husbandry, Amrita School of Agricultural Sciences, Amrita Vishwa Vidyapeetham University, Coimbatore 642109, India
| | - Talha Bin Emran
- Department of Pathology and Laboratory Medicine, Warren Alpert Medical School & Legorreta Cancer Center, Brown University, Providence, RI 02912, USA
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
- Department of Pharmacy, BGC Trust University Bangladesh, Chittagong 4381, Bangladesh
| | - Jesus Simal-Gandara
- Universidade de Vigo, Nutrition and Bromatology Group, Analytical Chemistry and Food Science Department, Faculty of Science, E32004 Ourense, Spain
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