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Ostrowska L, Smarkusz-Zarzecka J, Zyśk B, Orywal K, Mroczko B, Cwalina U. Could Selected Adipokines/Cytokines Serve as Markers of Adipose Tissue Dysfunction? Int J Mol Sci 2024; 25:13744. [PMID: 39769504 PMCID: PMC11677680 DOI: 10.3390/ijms252413744] [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: 12/04/2024] [Revised: 12/19/2024] [Accepted: 12/20/2024] [Indexed: 01/11/2025] Open
Abstract
Elevated levels of pro-inflammatory adipokines and cytokines increase the risk of developing metabolic disorders and diseases. The aim of this study was to conduct a comparative analysis of selected adipokines/cytokines in the blood serum of adults with obesity and normal body weight. The study also evaluated the correlation of these adipokines/cytokines with selected biochemical blood parameters. The study included 46 individuals with first- and second-degree obesity and 35 individuals with normal body weight. The participants underwent nutritional status assessments, biochemical tests, and evaluations of adipokine and cytokine concentrations in blood serum. The study found higher median CRP concentrations in women with obesity than in those with normal weight. This increase was statistically significant. The results also showed significantly higher IL-6 levels in the obesity group compared to the control group in both women and men. Resistin and MMP-2 were significantly different between women with obesity and women with normal body weight. Multiple regression results indicated that higher total fat content was significantly associated with higher serum CRP and IL-6 levels and lower adiponectin levels. Interleukin 6 was the strongest predictor of adipose tissue dysfunction in both women and men. Potential markers in women could also include resistin and MMP-2. The findings suggest that gender significantly influences the regulation of inflammatory factors.
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Affiliation(s)
- Lucyna Ostrowska
- Department of Dietetics and Clinical Nutrition, Medical University of Bialystok, ul. Mieszka I 4B, 15-054 Bialystok, Poland; (L.O.)
| | - Joanna Smarkusz-Zarzecka
- Department of Dietetics and Clinical Nutrition, Medical University of Bialystok, ul. Mieszka I 4B, 15-054 Bialystok, Poland; (L.O.)
| | - Beata Zyśk
- Department of Dietetics and Clinical Nutrition, Medical University of Bialystok, ul. Mieszka I 4B, 15-054 Bialystok, Poland; (L.O.)
| | - Karolina Orywal
- Department of Biochemical Diagnostics, Medical University of Bialystok, ul. Waszyngtona 15A, 15-269 Bialystok, Poland (B.M.)
| | - Barbara Mroczko
- Department of Biochemical Diagnostics, Medical University of Bialystok, ul. Waszyngtona 15A, 15-269 Bialystok, Poland (B.M.)
| | - Urszula Cwalina
- Department of Biostatistics and Medical Informatics, Medical University of Bialystok, ul. Szpitalna 37, 15-295 Bialystok, Poland;
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Kowalska K, Olejnik A. Rosehip Extract Decreases Reactive Oxygen Species Production and Lipid Accumulation in Hypertrophic 3T3-L1 Adipocytes with the Modulation of Inflammatory State. Nutrients 2024; 16:3269. [PMID: 39408236 PMCID: PMC11478984 DOI: 10.3390/nu16193269] [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: 08/09/2024] [Revised: 09/23/2024] [Accepted: 09/25/2024] [Indexed: 10/20/2024] Open
Abstract
BACKGROUND Rosa canina L. (rosehip) is used worldwide in traditional medicine as a plant with medicinal properties. However, its anti-obesity effects are not fully explained on a transcriptional level. METHODS In the present work, the 3T3-L preadipocytes were utilized to explore the impact of R. canina fruit extract (RCE) on the cellular and molecular pathways involved in adipocyte hypertrophy. RESULTS Obtained results showed the ability of RCE to reduce lipid overloads in hypertrophic adipocytes associated with the down-regulation of mRNA expressions of adipogenic transcription factors such as PPARγ, C/EBPα, and SREBP-1c as well as genes involved in lipid biosyntheses such as FAS, LPL, and aP2. Moreover, obesity-associated oxidative stress (antioxidant enzyme activities and ROS generation) and inflammation were ameliorated in RCE-treated hypertrophic adipocytes. The mRNA and protein levels of adipokines such as leptin, resistin, and adiponectin were restored to more favorable levels. CONCLUSIONS Rosa canina fruit might be a valuable source of phytochemicals in preventing obesity and obesity-related metabolic complications.
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Affiliation(s)
- Katarzyna Kowalska
- Department of Biotechnology and Food Microbiology, Poznan University of Life Sciences, 48 Wojska Polskiego St., 60-627 Poznan, Poland;
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Łukaszuk B, Supruniuk E, Chabowski A, Mikłosz A. Altered Cytokine Secretory Fingerprint of the Adipocytes Derived from Stem Cells of Morbidly Obese Patients-A Preliminary Study. Cells 2024; 13:1603. [PMID: 39404367 PMCID: PMC11475718 DOI: 10.3390/cells13191603] [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: 08/29/2024] [Revised: 09/18/2024] [Accepted: 09/23/2024] [Indexed: 10/19/2024] Open
Abstract
Context: Adipose-derived mesenchymal stem cells (ADMSCs) are progenitor cells that shape the tissue's biological properties. Objective: To examine the adipocytes differentiated from the ADMSCs of lean and obese individuals with/without a metabolic syndrome (MetSx) cytokine secretory profile, as to date, little is known on this topic. Methods: Interleukin, chemokine and growth factor levels in the culture medium were determined using the Human Cytokine kit. Results: We observed a characteristic secretory fingerprint displayed by the cells from the MetSx group and identified a set of putative markers (IL-1β, IL-6, IL-7, IL-10, IL-12, IL-13, VEGF, FGF, GM-CSF, TNF-α, IFN-γ) of the condition. Surprisingly, the concentrations of most of the molecules (except for IL-6, IFN-γ, IP-10, VEGF) decreased when compared with the cells from the lean group. We postulate that the difference stemmed from the fact that in vivo cytokines were mostly secreted by the activated monocytes/macrophages and not adipocytes per se. This may also suggest that the aforementioned upregulated cytokines (IL-6, IFN-γ, IP-10, VEGF) might have been the ones that attracted monocytes and triggered the vicious cycle of tissue inflammation. Conclusions: Our study indicated that the adipocytes newly derived from the ADMSCs of obese patients with metabolic syndrome displayed a secretory fingerprint that may be characteristic to the early stages of the condition.
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Affiliation(s)
- Bartłomiej Łukaszuk
- Department of Physiology, Medical University of Bialystok, 15-089 Bialystok, Poland; (E.S.); (A.M.)
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Han Y, Ye S, Liu B. Roles of extracellular vesicles derived from healthy and obese adipose tissue in inter-organ crosstalk and potential clinical implication. Front Endocrinol (Lausanne) 2024; 15:1409000. [PMID: 39268243 PMCID: PMC11390393 DOI: 10.3389/fendo.2024.1409000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Accepted: 08/12/2024] [Indexed: 09/15/2024] Open
Abstract
Extracellular vesicles (EVs) are nanovesicles containing bioactive molecules including proteins, nucleic acids and lipids that mediate intercellular and inter-organ communications, holding promise as potential therapeutics for multiple diseases. Adipose tissue (AT) serves as a dynamically distributed energy storage organ throughout the body, whose accumulation leads to obesity, a condition characterized by infiltration with abundant immune cells. Emerging evidence has illustrated that EVs secreted by AT are the novel class of adipokines that regulate the homeostasis between AT and peripheral organs. However, most of the studies focused on the investigations of EVs derived from adipocytes or adipose-derived stem cells (ADSCs), the summarization of functions in cellular and inter-organ crosstalk of EVs directly derived from adipose tissue (AT-EVs) are still limited. Here, we provide a systemic summary on the key components and functions of EVs derived from healthy adipose tissue, showing their significance on the tissue recovery and metabolic homeostasis regulation. Also, we discuss the harmful influences of EVs derived from obese adipose tissue on the distal organs. Furthermore, we elucidate the potential applications and constraints of EVs from healthy patients lipoaspirates as therapeutic agents, highlighting the potential of AT-EVs as a valuable biological material with broad prospects for future clinical use.
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Affiliation(s)
- Yue Han
- School of Engineering Medicine, Beihang University, Beijing, China
- Key Laboratory of Big Data-based Precision Medicine (Beihang University), Ministry of Industry and Information Technology, Beijing, China
| | - Sheng Ye
- School of Engineering Medicine, Beihang University, Beijing, China
- Key Laboratory of Big Data-based Precision Medicine (Beihang University), Ministry of Industry and Information Technology, Beijing, China
| | - Bowen Liu
- School of Medicine, The Chinese University of Hong Kong, Shenzhen, Guangdong, China
- School of Life Sciences, Westlake University, Hangzhou, China
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Elkanawati RY, Sumiwi SA, Levita J. Impact of Lipids on Insulin Resistance: Insights from Human and Animal Studies. Drug Des Devel Ther 2024; 18:3337-3360. [PMID: 39100221 PMCID: PMC11298177 DOI: 10.2147/dddt.s468147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Accepted: 07/24/2024] [Indexed: 08/06/2024] Open
Abstract
Insulin resistance (IR) is a complex pathological condition central to metabolic diseases such as type 2 diabetes mellitus (T2DM), cardiovascular disease, non-alcoholic fatty liver disease, and polycystic ovary syndrome (PCOS). This review evaluates the impact of lipids on insulin resistance (IR) by analyzing findings from human and animal studies. The articles were searched on the PubMed database using two keywords: (1) "Role of Lipids AND Insulin Resistance AND Humans" and (2) "Role of Lipids AND Insulin Resistance AND Animal Models". Studies in humans revealed that elevated levels of free fatty acids (FFAs) and triglycerides (TGs) are closely associated with reduced insulin sensitivity, and interventions like metformin and omega-3 fatty acids show potential benefits. In animal models, high-fat diets disrupt insulin signaling and increase inflammation, with lipid mediators such as diacylglycerol (DAG) and ceramides playing significant roles. DAG activates protein kinase C, which eventually impairs insulin signaling, while ceramides inhibit Akt/PKB, further contributing to IR. Understanding these mechanisms is crucial for developing effective prevention and treatment strategies for IR-related diseases.
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Affiliation(s)
- Rani Yulifah Elkanawati
- Master Program in Pharmacy, Faculty of Pharmacy, Padjadjaran University, Jawa Barat, West Java, 45363, Indonesia
| | - Sri Adi Sumiwi
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Padjadjaran University, Sumedang, West Java, 45363, Indonesia
| | - Jutti Levita
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Padjadjaran University, Sumedang, West Java, 45363, Indonesia
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Bettinetti-Luque M, Trujillo-Estrada L, Garcia-Fuentes E, Andreo-Lopez J, Sanchez-Varo R, Garrido-Sánchez L, Gómez-Mediavilla Á, López MG, Garcia-Caballero M, Gutierrez A, Baglietto-Vargas D. Adipose tissue as a therapeutic target for vascular damage in Alzheimer's disease. Br J Pharmacol 2024; 181:840-878. [PMID: 37706346 DOI: 10.1111/bph.16243] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 08/11/2023] [Accepted: 09/01/2023] [Indexed: 09/15/2023] Open
Abstract
Adipose tissue has recently been recognized as an important endocrine organ that plays a crucial role in energy metabolism and in the immune response in many metabolic tissues. With this regard, emerging evidence indicates that an important crosstalk exists between the adipose tissue and the brain. However, the contribution of adipose tissue to the development of age-related diseases, including Alzheimer's disease, remains poorly defined. New studies suggest that the adipose tissue modulates brain function through a range of endogenous biologically active factors known as adipokines, which can cross the blood-brain barrier to reach the target areas in the brain or to regulate the function of the blood-brain barrier. In this review, we discuss the effects of several adipokines on the physiology of the blood-brain barrier, their contribution to the development of Alzheimer's disease and their therapeutic potential. LINKED ARTICLES: This article is part of a themed issue From Alzheimer's Disease to Vascular Dementia: Different Roads Leading to Cognitive Decline. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.6/issuetoc.
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Affiliation(s)
- Miriam Bettinetti-Luque
- Departamento de Biología Celular, Genética y Fisiología, Instituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma BIONAND, Facultad de Ciencias, Universidad de Málaga, Málaga, Spain
| | - Laura Trujillo-Estrada
- Departamento de Biología Celular, Genética y Fisiología, Instituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma BIONAND, Facultad de Ciencias, Universidad de Málaga, Málaga, Spain
- CIBER de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain
| | - Eduardo Garcia-Fuentes
- Unidad de Gestión Clínica Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma BIONAND, Málaga, Spain
- CIBER de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain
| | - Juana Andreo-Lopez
- Departamento de Biología Celular, Genética y Fisiología, Instituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma BIONAND, Facultad de Ciencias, Universidad de Málaga, Málaga, Spain
| | - Raquel Sanchez-Varo
- Departamento de Biología Celular, Genética y Fisiología, Instituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma BIONAND, Facultad de Ciencias, Universidad de Málaga, Málaga, Spain
- CIBER de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain
- Departamento de Fisiología Humana, Histología Humana, Anatomía Patológica y Educación Física y Deportiva, Facultad de Medicina, Universidad de Málaga, Málaga, Spain
| | - Lourdes Garrido-Sánchez
- CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
- Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma BIONAND, Málaga, Spain
| | - Ángela Gómez-Mediavilla
- Departamento de Farmacología, Facultad de Medicina. Instituto Teófilo Hernando para la I+D de Fármacos, Universidad Autónoma de Madrid, Madrid, Spain
| | - Manuela G López
- Departamento de Farmacología, Facultad de Medicina. Instituto Teófilo Hernando para la I+D de Fármacos, Universidad Autónoma de Madrid, Madrid, Spain
- Instituto de Investigaciones Sanitarias (IIS-IP), Hospital Universitario de la Princesa, Madrid, Spain
| | - Melissa Garcia-Caballero
- Departamento de Biología Molecular y Bioquímica, Instituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma BIONAND, Facultad de Ciencias, Universidad de Málaga, Málaga, Spain
| | - Antonia Gutierrez
- Departamento de Biología Celular, Genética y Fisiología, Instituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma BIONAND, Facultad de Ciencias, Universidad de Málaga, Málaga, Spain
- CIBER de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain
| | - David Baglietto-Vargas
- Departamento de Biología Celular, Genética y Fisiología, Instituto de Investigación Biomédica de Málaga (IBIMA)-Plataforma BIONAND, Facultad de Ciencias, Universidad de Málaga, Málaga, Spain
- CIBER de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain
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Gupta A, Gupta P, Singh AK, Gupta V. Association of adipokines with insulin resistance and metabolic syndrome including obesity and diabetes. GHM OPEN 2023; 3:7-19. [PMID: 40143837 PMCID: PMC11933950 DOI: 10.35772/ghmo.2023.01004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 07/18/2023] [Accepted: 07/25/2023] [Indexed: 03/28/2025]
Abstract
Adipose tissue (AT) acts as a highly active endocrine organ, which secretes a wide range of adipokine hormones. In the past few years, several adipokines (leptin, adiponectin, resistin etc.) have been discovered showing metabolic consequences in relation to insulin resistance (IR), obesity and diabetes. These adipokines are considered to be an important component playing an important role in the regulation of energy metabolism. They have been shown to be involved in the pathogenesis of metabolic syndrome (MetS) and cardiac diseases. The current article provides a holistic summary of recent knowledge on adipokines and emphasizes their importance in association with IR, obesity, diabetes and MetS. Adipokines such as leptin, adiponectin, resistin and tumor necrosis factor-alpha (TNF-α) have been involved in the regulation of an array of metabolic functions and disease associated with it, e.g. appetite and energy balance of the body, suppression of atherosclerosis and liver fibrosis, obesity with type 2 diabetes (T2D) and IR. An important adipokine, Interleukin-6 (IL-6), also correlates positively with human obesity and IR and also the elevated level of IL-6 predicts development of T2D. All of these hormones have important correlation with energy homeostasis, glucose and lipid metabolism, cardiovascular function and immunity. All the possible connections have extended the biological emphasis of AT secreted adipokines as an investigator in the development of MetS, and are now no longer considered as only an energy storage site.
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Affiliation(s)
- Abhishek Gupta
- Department of Physiology, King George's Medical University, Lucknow, India
| | - Priyanka Gupta
- Department of Medicine, King George's Medical University, Lucknow, India
| | - Arun Kumar Singh
- Department of Physiology, King George's Medical University, Lucknow, India
| | - Vani Gupta
- Department of Physiology, King George's Medical University, Lucknow, India
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Lempesis IG, Georgakopoulou VE. Physiopathological mechanisms related to inflammation in obesity and type 2 diabetes mellitus. World J Exp Med 2023; 13:7-16. [PMID: 37396883 PMCID: PMC10308320 DOI: 10.5493/wjem.v13.i3.7] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Revised: 02/15/2023] [Accepted: 04/10/2023] [Indexed: 06/16/2023] Open
Abstract
Overweight, obesity, and type 2 diabetes mellitus pose global health problems that are ever-increasing. A chronic low-grade inflammatory status and the presence of various pro-inflammatory markers either in circulation or within dysfunctional metabolic tissues are well established. The presence of these factors can, to some extent, predict disease development and progression. A central role is played by the presence of dysfunctional adipose tissue, liver dysfunction, and skeletal muscle dysfunction, which collectively contribute to the increased circulatory levels of proinflammatory factors. Weight loss and classical metabolic interventions achieve a decrease in many of these factors' circulating levels, implying that a better understanding of the processes or even the modulation of inflammation may alleviate these diseases. This review suggests that inflammation plays a significant role in the development and progression of these conditions and that measuring inflammatory markers may be useful for assessing disease risk and development of future treatment methods.
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Affiliation(s)
- Ioannis G Lempesis
- Department of Infectious Diseases-COVID-19 Unit, Laiko General Hospital, Athens 11527, Greece
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Abdallah YEH, Chahal S, Jamali F, Mahmoud SH. Drug-disease interaction: Clinical consequences of inflammation on drugs action and disposition. JOURNAL OF PHARMACY & PHARMACEUTICAL SCIENCES : A PUBLICATION OF THE CANADIAN SOCIETY FOR PHARMACEUTICAL SCIENCES, SOCIETE CANADIENNE DES SCIENCES PHARMACEUTIQUES 2023; 26:11137. [PMID: 36942294 PMCID: PMC9990632 DOI: 10.3389/jpps.2023.11137] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Accepted: 01/23/2023] [Indexed: 02/07/2023]
Abstract
Inflammation is a culprit in many conditions affecting millions of people worldwide. A plethora of studies has revealed that inflammation and inflammatory mediators such as cytokines and chemokines are associated with altered expression and activity of various proteins such as those involved in drug metabolism, specifically cytochrome P450 enzymes (CYPs). Emphasis of most available reports is on the inflammation-induced downregulation of CYPs, subsequently an increase in their substrate concentrations, and the link between the condition and the inflammatory mediators such as interleukin-6 and tumor necrosis factor alpha. However, reports also suggest that inflammation influences expression and/or activity of other proteins such as those involved in the drug-receptor interaction. These multifaced involvements render the clinical consequence of the inflammation unexpected. Such changes are shown in many inflammatory conditions including rheumatoid arthritis, Crohn's disease, acute respiratory illnesses as well as natural processes such as aging, among others. For example, some commonly used cardiovascular drugs lose their efficacy when patients get afflicted with inflammatory conditions such as rheumatoid arthritis and Crohn's disease. Interestingly, this is despite increased concentration subsequent to reduced clearance. The observation is attributed to a simultaneous reduction in the expression of target receptor proteins such as the calcium and potassium channel and β-adrenergic receptor as well as the metabolic enzymes. This narrative review summarizes the current understanding and clinical implications of the inflammatory effects on both CYPs and drug-receptor target proteins.
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Jiang Z, Qu H, Chen K, Gao Z. Beneficial effects of folic acid on inflammatory markers in the patients with metabolic syndrome: Meta-analysis and meta-regression of data from 511 participants in 10 randomized controlled trials. Crit Rev Food Sci Nutr 2022; 64:5450-5461. [PMID: 36576260 DOI: 10.1080/10408398.2022.2154743] [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: 12/29/2022]
Abstract
Previous clinical studies on the anti-inflammatory effects of folic acid (FA) in patients with metabolic syndrome (MetS) have shown controversial results. This study aimed to synthesize the evidence on the effect of FA on inflammatory marker levels in MetS patients. We screened PubMed, Embase, Medline, and the Cochrane Library (from inception to March 2022) to identify relevant randomized controlled trials (RCTs). DerSimonian and Laird random effects were used to estimate the pooled weighted mean difference (WMD) with 95% confidence interval (CI). Funnel plot, Egger's test, and the Begg-Mazumdar correlation test was used to assess publication bias. Subgroup analysis, meta-regression and sensitivity analysis were performed to find out possible sources of between-study heterogeneity. Ten RCTs with a total of 511 participants were included. The analysis showed that FA reduced high sensitivity C-reactive protein (hs-CRP) (WMD, -0.94; 95% CI, -1.56 to -0.32; P = 0.00), interleukin-6 (IL-6) (WMD, -0.39; 95% CI, -0.51 to -0.28; P = 0.00), and tumor necrosis factor-alpha (TNF-α) (WMD, -1.28; 95% CI, -1.88 to -0.68; P = 0.00), but did not decrease the C-reactive protein (CRP) (WMD, 0.10; 95% CI, -0.13 to 0.33; P = 0.38). Sensitivity analysis, subgroup analysis, and meta-regression showed that the effect sizes remained stable. Our findings suggest that FA supplementation could reduce inflammatory markers, such as hs-CRP, IL-6, TNF-α in patients with MetS. This study is registered with PROSPERO (CRD42021223843).
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Affiliation(s)
- Zhonghui Jiang
- Department of Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- National Clinical Research Center for Chinese Medicine Cardiology, Beijing, China
| | - Hua Qu
- Department of Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- National Clinical Research Center for Chinese Medicine Cardiology, Beijing, China
| | - Keji Chen
- Department of Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- National Clinical Research Center for Chinese Medicine Cardiology, Beijing, China
| | - Zhuye Gao
- Department of Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- National Clinical Research Center for Chinese Medicine Cardiology, Beijing, China
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Tatoli R, Lampignano L, Donghia R, Castellana F, Zupo R, Bortone I, De Nucci S, Campanile G, Lofù D, Vimercati L, Lozupone M, De Pergola G, Panza F, Giannelli G, Di Noia T, Boeing H, Sardone R. Dietary Customs and Social Deprivation in an Aging Population From Southern Italy: A Machine Learning Approach. Front Nutr 2022; 9:811076. [PMID: 35340551 PMCID: PMC8942783 DOI: 10.3389/fnut.2022.811076] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Accepted: 02/10/2022] [Indexed: 12/20/2022] Open
Abstract
Background Diet and social determinants influence the state of human health. In older adults, the presence of social, physical and psychological barriers increases the probability of deprivation. This study investigated the relationship between social deprivation and eating habits in non-institutionalized older adults from Southern Italy, and identified foods and dietary habits associated with social deprivation. Methods We recruited 1,002 subjects, mean age 74 years, from the large population based Salus in Apulia Study. In this cross-sectional study, eating habits and the level of deprivation were assessed with FFQ and DiPCare-Q, respectively. Results Deprived subjects (n = 441) included slightly more females, who were slightly older and with a lower level of education. They consumed less fish (23 vs. 26 g), fruiting vegetables (87 vs. 102 g), nuts (6 vs. 9 g) and less “ready to eat” dishes (29 vs. 33 g). A Random Forest (RF) model was used to identify a dietary pattern associated with social deprivation. This pattern included an increased consumption of low-fat dairy products and white meat, and a decreased consumption of wine, leafy vegetables, seafood/shellfish, processed meat, red meat, dairy products, and eggs. Conclusion The present study showed that social factors also define diet and eating habits. Subjects with higher levels of deprivation consume cheaper and more readily available food.
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Affiliation(s)
- Rossella Tatoli
- Unit of Digital Health and Health Technology Assessment for "Salus in Apulia Study," National Institute of Gastroenterology, "S. de Bellis" Research Hospital, Castellana Grotte, Italy
| | - Luisa Lampignano
- Unit of Digital Health and Health Technology Assessment for "Salus in Apulia Study," National Institute of Gastroenterology, "S. de Bellis" Research Hospital, Castellana Grotte, Italy
| | - Rossella Donghia
- Unit of Digital Health and Health Technology Assessment for "Salus in Apulia Study," National Institute of Gastroenterology, "S. de Bellis" Research Hospital, Castellana Grotte, Italy
| | - Fabio Castellana
- Unit of Digital Health and Health Technology Assessment for "Salus in Apulia Study," National Institute of Gastroenterology, "S. de Bellis" Research Hospital, Castellana Grotte, Italy
| | - Roberta Zupo
- Unit of Digital Health and Health Technology Assessment for "Salus in Apulia Study," National Institute of Gastroenterology, "S. de Bellis" Research Hospital, Castellana Grotte, Italy
| | - Ilaria Bortone
- Unit of Digital Health and Health Technology Assessment for "Salus in Apulia Study," National Institute of Gastroenterology, "S. de Bellis" Research Hospital, Castellana Grotte, Italy
| | - Sara De Nucci
- Unit of Digital Health and Health Technology Assessment for "Salus in Apulia Study," National Institute of Gastroenterology, "S. de Bellis" Research Hospital, Castellana Grotte, Italy
| | - Giuseppe Campanile
- Unit of Digital Health and Health Technology Assessment for "Salus in Apulia Study," National Institute of Gastroenterology, "S. de Bellis" Research Hospital, Castellana Grotte, Italy
| | - Domenico Lofù
- Department of Electrical and Information Engineering, Polytechnic of Bari, Bari, Italy
| | - Luigi Vimercati
- Interdisciplinary Department of Medicine, Section of Occupational Medicine B. Ramazzini, School of Medicine, University of Bari Aldo Moro, Bari, Italy
| | - Madia Lozupone
- Department of Basic Medicine, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Bari, Italy
| | - Giovanni De Pergola
- Unit of Internal Medicine and Geriatrics, National Institute of Gastroenterology "S. de Bellis" Research Hospital, Castellana Grotte, Italy.,Department of Biomedical Science and Human Oncology, School of Medicine, University of Bari Aldo Moro, Bari, Italy
| | - Francesco Panza
- Department of Basic Medicine, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Bari, Italy
| | - Gianluigi Giannelli
- Unit of Digital Health and Health Technology Assessment for "Salus in Apulia Study," National Institute of Gastroenterology, "S. de Bellis" Research Hospital, Castellana Grotte, Italy
| | - Tommaso Di Noia
- Department of Electrical and Information Engineering, Polytechnic of Bari, Bari, Italy
| | - Heiner Boeing
- Unit of Digital Health and Health Technology Assessment for "Salus in Apulia Study," National Institute of Gastroenterology, "S. de Bellis" Research Hospital, Castellana Grotte, Italy.,Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
| | - Rodolfo Sardone
- Unit of Digital Health and Health Technology Assessment for "Salus in Apulia Study," National Institute of Gastroenterology, "S. de Bellis" Research Hospital, Castellana Grotte, Italy
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12
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Tatoli R, Lampignano L, Bortone I, Donghia R, Castellana F, Zupo R, Tirelli S, De Nucci S, Sila A, Natuzzi A, Lozupone M, Griseta C, Sciarra S, Aresta S, De Pergola G, Sorino P, Lofù D, Panza F, Di Noia T, Sardone R. Dietary Patterns Associated with Diabetes in an Older Population from Southern Italy Using an Unsupervised Learning Approach. SENSORS 2022; 22:s22062193. [PMID: 35336365 PMCID: PMC8949084 DOI: 10.3390/s22062193] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Revised: 03/04/2022] [Accepted: 03/08/2022] [Indexed: 01/27/2023]
Abstract
Dietary behaviour is a core element in diabetes self-management. There are no remarkable differences between nutritional guidelines for people with type 2 diabetes and healthy eating recommendations for the general public. This study aimed to evaluate dietary differences between subjects with and without diabetes and to describe any emerging dietary patterns characterizing diabetic subjects. In this cross-sectional study conducted on older adults from Southern Italy, eating habits in the “Diabetic” and “Not Diabetic” groups were assessed with FFQ, and dietary patterns were derived using an unsupervised learning algorithm: principal component analysis. Diabetic subjects (n = 187) were more likely to be male, slightly older, and with a slightly lower level of education than subjects without diabetes. The diet of diabetic subjects reflected a high-frequency intake of dairy products, eggs, vegetables and greens, fresh fruit and nuts, and olive oil. On the other hand, the consumption of sweets and sugary foods was reduced compared to non-diabetics (23.74 ± 35.81 vs. 16.52 ± 22.87; 11.08 ± 21.85 vs. 7.22 ± 15.96). The subjects without diabetes had a higher consumption of red meat, processed meat, ready-to-eat dishes, alcoholic drinks, and lower vegetable consumption. The present study demonstrated that, in areas around the Mediterranean Sea, older subjects with diabetes had a healthier diet than their non-diabetic counterparts.
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Affiliation(s)
- Rossella Tatoli
- Unit of Data Sciences and Technology Innovation for Population Health, National Institute of Gastroenterology “Saverio de Bellis”, Research Hospital, 70013 Bari, Italy; (R.T.); (R.D.); (F.C.); (R.Z.); (S.T.); (S.D.N.); (A.S.); (A.N.); (C.G.); (S.S.); (S.A.); (R.S.)
| | - Luisa Lampignano
- Unit of Data Sciences and Technology Innovation for Population Health, National Institute of Gastroenterology “Saverio de Bellis”, Research Hospital, 70013 Bari, Italy; (R.T.); (R.D.); (F.C.); (R.Z.); (S.T.); (S.D.N.); (A.S.); (A.N.); (C.G.); (S.S.); (S.A.); (R.S.)
- Correspondence: (L.L.); (I.B.)
| | - Ilaria Bortone
- Unit of Data Sciences and Technology Innovation for Population Health, National Institute of Gastroenterology “Saverio de Bellis”, Research Hospital, 70013 Bari, Italy; (R.T.); (R.D.); (F.C.); (R.Z.); (S.T.); (S.D.N.); (A.S.); (A.N.); (C.G.); (S.S.); (S.A.); (R.S.)
- Correspondence: (L.L.); (I.B.)
| | - Rossella Donghia
- Unit of Data Sciences and Technology Innovation for Population Health, National Institute of Gastroenterology “Saverio de Bellis”, Research Hospital, 70013 Bari, Italy; (R.T.); (R.D.); (F.C.); (R.Z.); (S.T.); (S.D.N.); (A.S.); (A.N.); (C.G.); (S.S.); (S.A.); (R.S.)
| | - Fabio Castellana
- Unit of Data Sciences and Technology Innovation for Population Health, National Institute of Gastroenterology “Saverio de Bellis”, Research Hospital, 70013 Bari, Italy; (R.T.); (R.D.); (F.C.); (R.Z.); (S.T.); (S.D.N.); (A.S.); (A.N.); (C.G.); (S.S.); (S.A.); (R.S.)
| | - Roberta Zupo
- Unit of Data Sciences and Technology Innovation for Population Health, National Institute of Gastroenterology “Saverio de Bellis”, Research Hospital, 70013 Bari, Italy; (R.T.); (R.D.); (F.C.); (R.Z.); (S.T.); (S.D.N.); (A.S.); (A.N.); (C.G.); (S.S.); (S.A.); (R.S.)
| | - Sarah Tirelli
- Unit of Data Sciences and Technology Innovation for Population Health, National Institute of Gastroenterology “Saverio de Bellis”, Research Hospital, 70013 Bari, Italy; (R.T.); (R.D.); (F.C.); (R.Z.); (S.T.); (S.D.N.); (A.S.); (A.N.); (C.G.); (S.S.); (S.A.); (R.S.)
| | - Sara De Nucci
- Unit of Data Sciences and Technology Innovation for Population Health, National Institute of Gastroenterology “Saverio de Bellis”, Research Hospital, 70013 Bari, Italy; (R.T.); (R.D.); (F.C.); (R.Z.); (S.T.); (S.D.N.); (A.S.); (A.N.); (C.G.); (S.S.); (S.A.); (R.S.)
| | - Annamaria Sila
- Unit of Data Sciences and Technology Innovation for Population Health, National Institute of Gastroenterology “Saverio de Bellis”, Research Hospital, 70013 Bari, Italy; (R.T.); (R.D.); (F.C.); (R.Z.); (S.T.); (S.D.N.); (A.S.); (A.N.); (C.G.); (S.S.); (S.A.); (R.S.)
| | - Annalidia Natuzzi
- Unit of Data Sciences and Technology Innovation for Population Health, National Institute of Gastroenterology “Saverio de Bellis”, Research Hospital, 70013 Bari, Italy; (R.T.); (R.D.); (F.C.); (R.Z.); (S.T.); (S.D.N.); (A.S.); (A.N.); (C.G.); (S.S.); (S.A.); (R.S.)
| | - Madia Lozupone
- Neurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense Organs, University of Bari Aldo Moro, 11, 70125 Bari, Italy; (M.L.); (F.P.)
| | - Chiara Griseta
- Unit of Data Sciences and Technology Innovation for Population Health, National Institute of Gastroenterology “Saverio de Bellis”, Research Hospital, 70013 Bari, Italy; (R.T.); (R.D.); (F.C.); (R.Z.); (S.T.); (S.D.N.); (A.S.); (A.N.); (C.G.); (S.S.); (S.A.); (R.S.)
| | - Sabrina Sciarra
- Unit of Data Sciences and Technology Innovation for Population Health, National Institute of Gastroenterology “Saverio de Bellis”, Research Hospital, 70013 Bari, Italy; (R.T.); (R.D.); (F.C.); (R.Z.); (S.T.); (S.D.N.); (A.S.); (A.N.); (C.G.); (S.S.); (S.A.); (R.S.)
| | - Simona Aresta
- Unit of Data Sciences and Technology Innovation for Population Health, National Institute of Gastroenterology “Saverio de Bellis”, Research Hospital, 70013 Bari, Italy; (R.T.); (R.D.); (F.C.); (R.Z.); (S.T.); (S.D.N.); (A.S.); (A.N.); (C.G.); (S.S.); (S.A.); (R.S.)
| | - Giovanni De Pergola
- Unit of Geriatrics and Internal Medicine, National Institute of Gastroenterology “Saverio de Bellis”, Research Hospital, 70013 Bari, Italy;
| | - Paolo Sorino
- Department of Electrical and Information Engineering, Polytechnic of Bari, 70125 Bari, Italy; (P.S.); (D.L.); (T.D.N.)
| | - Domenico Lofù
- Department of Electrical and Information Engineering, Polytechnic of Bari, 70125 Bari, Italy; (P.S.); (D.L.); (T.D.N.)
| | - Francesco Panza
- Neurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense Organs, University of Bari Aldo Moro, 11, 70125 Bari, Italy; (M.L.); (F.P.)
| | - Tommaso Di Noia
- Department of Electrical and Information Engineering, Polytechnic of Bari, 70125 Bari, Italy; (P.S.); (D.L.); (T.D.N.)
| | - Rodolfo Sardone
- Unit of Data Sciences and Technology Innovation for Population Health, National Institute of Gastroenterology “Saverio de Bellis”, Research Hospital, 70013 Bari, Italy; (R.T.); (R.D.); (F.C.); (R.Z.); (S.T.); (S.D.N.); (A.S.); (A.N.); (C.G.); (S.S.); (S.A.); (R.S.)
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13
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Steele C, Nowak K. Obesity, Weight Loss, Lifestyle Interventions, and Autosomal Dominant Polycystic Kidney Disease. KIDNEY AND DIALYSIS 2022; 2:106-122. [PMID: 35350649 PMCID: PMC8959086 DOI: 10.3390/kidneydial2010013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/09/2023]
Abstract
Obesity remains a growing public health concern in industrialized countries around the world. The prevalence of obesity has also continued to rise in those with chronic kidney disease. Epidemiological data suggests those with overweight and obesity, measured by body mass index, have an increased risk for rapid kidney disease progression. Autosomal dominant polycystic kidney disease causes growth and proliferation of kidney cysts resulting in a reduction in kidney function in the majority of adults. An accumulation of adipose tissue may further exacerbate the metabolic defects that have been associated with ADPKD by affecting various cell signaling pathways. Lifestyle interventions inducing weight loss might help delay disease progression by reducing adipose tissue and systematic inflammation. Further research is needed to determine the mechanistic influence of adipose tissue on disease progression.
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Affiliation(s)
- Cortney Steele
- Division of Renal Diseases and Hypertension, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA
| | - Kristen Nowak
- Division of Renal Diseases and Hypertension, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA
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14
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Jiang Z, Qu H, Lin G, Shi D, Chen K, Gao Z. Lipid-Lowering Efficacy of the Capsaicin in Patients With Metabolic Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Front Nutr 2022; 9:812294. [PMID: 35299764 PMCID: PMC8923259 DOI: 10.3389/fnut.2022.812294] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 01/31/2022] [Indexed: 12/28/2022] Open
Abstract
Background Patients with metabolic syndrome (MetS) have increased cardiovascular risk. Capsaicin (CAP) has been shown to reduce lipids, but efficacy for patients with MetS is unknown. Methods A systematic review was performed according to PRISMA guidelines, to compare the effects of CAP against a placebo. Differences in the weight mean difference (WMD) with 95% confidence intervals (95% CI) were then pooled using a random effects model. Results Nine randomized controlled trials including 461 patients were identified in the overall analysis. CAP significantly decreased total cholesterol (TC) (WMD = −0.48, 95% CI: −0.63 to −0.34, I2= 0.00%) and low-density lipoprotein cholesterol (LDL-C) (WMD = −0.23, 95% CI: −0.45 to −0.02, I2 = 68.27%) among patients with MetS. No significant effects of CAP were found on triglycerides (TG) or high-density lipoprotein cholesterol (HDL-C) (WMD = −0.40, 95% CI: −1.50 to 0.71, I2 = 98.32%; WMD = −0.08, 95% CI: −0.21 to 0.04, I2 = 86.06%). Subgroup analyses indicated that sex and intervention period were sources of heterogeneity. The results revealed that CAP decreased TG levels in women (WMD = −0.59, 95% CI: −1.07 to −0.10) and intervention period <12 weeks (WMD = −0.65; 95% CI: −1.10 to −0.20). And there was no potential publication bias according to funnel plot, Begg' test and Egger regression test. Conclusions CAP supplementation is a promising approach to decreasing TC and LCL-C levels in patients with MetS. However, short-term (<12 weeks) use of CAP in women may also reduce TG levels. Systematic Review Registration Identifier: CRD42021228032.
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Affiliation(s)
- Zhonghui Jiang
- Department of Cardiology, China Academy of Chinese Medical Sciences, Xiyuan Hospital, Beijing, China
- National Clinical Research Center for Chinese Medicine Cardiology, Beijing, China
| | - Hua Qu
- Department of Cardiology, China Academy of Chinese Medical Sciences, Xiyuan Hospital, Beijing, China
- National Clinical Research Center for Chinese Medicine Cardiology, Beijing, China
| | - Gongyu Lin
- Department of Cardiology, China Academy of Chinese Medical Sciences, Xiyuan Hospital, Beijing, China
- National Clinical Research Center for Chinese Medicine Cardiology, Beijing, China
- Department of Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Dazhuo Shi
- Department of Cardiology, China Academy of Chinese Medical Sciences, Xiyuan Hospital, Beijing, China
- National Clinical Research Center for Chinese Medicine Cardiology, Beijing, China
| | - Keji Chen
- Department of Cardiology, China Academy of Chinese Medical Sciences, Xiyuan Hospital, Beijing, China
- National Clinical Research Center for Chinese Medicine Cardiology, Beijing, China
- *Correspondence: Keji Chen
| | - Zhuye Gao
- Department of Cardiology, China Academy of Chinese Medical Sciences, Xiyuan Hospital, Beijing, China
- National Clinical Research Center for Chinese Medicine Cardiology, Beijing, China
- Zhuye Gao
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15
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Iijima Y, Ishikawa M, Iwai S, Yamagata A, Motono N, Uramoto H. Is Overweight Related to the Prognosis of Octogenarians with Lung Cancer? Obes Surg 2022; 32:1279-1288. [DOI: 10.1007/s11695-022-05948-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Revised: 02/02/2022] [Accepted: 02/03/2022] [Indexed: 10/19/2022]
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16
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Murakami S, Hirazawa C, Yoshikawa R, Mizutani T, Ohya T, Ma N, Ikemori T, Ito T, Matsuzaki C. Edible red seaweed Campylaephora hypnaeoides J. Agardh alleviates obesity and related metabolic disorders in mice by suppressing oxidative stress and inflammatory response. Nutr Metab (Lond) 2022; 19:4. [PMID: 34998411 PMCID: PMC8742934 DOI: 10.1186/s12986-021-00633-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Accepted: 11/30/2021] [Indexed: 12/11/2022] Open
Abstract
Background The obesity epidemic has become a serious public health problem in many countries worldwide. Seaweed has few calories and is rich in active nutritional components necessary for health promotion and disease prevention. The aim of this study was to investigate the effects of the Campylaephora hypnaeoides J. Agardh (C. hypnaeoides), an edible seaweed traditionally eaten in Japan, on high-fat (HF) diet-induced obesity and related metabolic diseases in mice. Methods Male C57BL/6J mice were randomly divided into the following groups: normal diet group, HF diet group, HF diet supplemented with 2% C. hypnaeoides, and HF diet supplemented with 6% C. hypnaeoides. After 13 weeks of treatment, the weight of the white adipose tissue and liver, and the serum levels of glucose, insulin, adipokines, and lipids were measured. Hepatic levels of adipokines, oxidant markers, and antioxidant markers were also determined. Insulin resistance was assessed by a glucose tolerance test. Polysaccharides of C. hypnaeoides were purified and their molecular weight was determined by high-performance seize exclusion chromatography. The anti-inflammatory effects of purified polysaccharides were evaluated in RAW264.7 cells. Results Treatment of HF diet-induced obese mice with C. hypnaeoides for 13 weeks suppressed the increase in body weight and white adipose tissue weight. It also ameliorated insulin resistance, hyperglycemia, hepatic steatosis, and hypercholesterolemia. The ingestion of an HF diet increased serum levels of malondialdehyde (MDA), tumor necrosis factor α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1), while it decreased serum adiponectin levels. In the liver, an HF diet markedly increased the MDA, TNF-α, and interleukin-6 (IL-6) levels, while it decreased glutathione and superoxide dismutase. These metabolic changes induced by HF diet feeding were ameliorated by dietary C. hypnaeoides. Purified polysaccharides and ethanol extract from C. hypnaeoides inhibited the lipopolysaccharide-induced overproduction of nitric oxide and TNF-α in macrophage RAW264.7 cells. Conclusions The present results indicated that C. hypnaeoides was able to alleviate HF diet-induced metabolic disorders, including obesity, hyperglycemia, hepatic steatosis, and hypercholesterolemia by attenuating inflammation and improving the antioxidant capacity in mice. Polysaccharides and polyphenols may be involved in these beneficial effects of C. hypnaeoides.
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Affiliation(s)
- Shigeru Murakami
- Department of Bioscience and Biotechnology, Fukui Prefectural University, Fukui, 9101195, Japan.
| | - Chihiro Hirazawa
- Department of Bioscience and Biotechnology, Fukui Prefectural University, Fukui, 9101195, Japan
| | - Rina Yoshikawa
- Department of Bioscience and Biotechnology, Fukui Prefectural University, Fukui, 9101195, Japan
| | - Toshiki Mizutani
- Department of Bioscience and Biotechnology, Fukui Prefectural University, Fukui, 9101195, Japan
| | - Takuma Ohya
- Department of Bioscience and Biotechnology, Fukui Prefectural University, Fukui, 9101195, Japan
| | - Ning Ma
- Division of Health Science, Graduate School of Health Science, Suzuka University, Mie, 5100293, Japan
| | - Takahiko Ikemori
- Ishikawa Prefecture Fisheries Division, Ishikawa, 9208580, Japan
| | - Takashi Ito
- Department of Bioscience and Biotechnology, Fukui Prefectural University, Fukui, 9101195, Japan
| | - Chiaki Matsuzaki
- Research Institute for Bioscience and Biotechnology, Ishikawa Prefectural University, Ishikawa, 9218836, Japan
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Subramanian N, Tavira B, Hofwimmer K, Gutsmann B, Massier L, Abildgaard J, Juul A, Rydén M, Arner P, Laurencikiene J. Sex-specific regulation of IL-10 production in human adipose tissue in obesity. Front Endocrinol (Lausanne) 2022; 13:996954. [PMID: 36313784 PMCID: PMC9606404 DOI: 10.3389/fendo.2022.996954] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Accepted: 09/20/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Obesity-associated metabolic complications display sexual dimorphism and can be impacted by cytokines. We previously showed that interleukin-10 (IL-10) was upregulated in white adipose tissue (WAT) of obese women with type 2 diabetes (T2D). Whether this pertains to men is unknown. The aim of this study was to compare the impact of obesity and T2D on WAT IL-10 levels in men versus women. METHODS Plasma and subcutaneous WAT biopsies were obtained from 108 metabolically well-characterized individuals. WAT IL10 expression/secretion and WAT-resident IL-10-secreting macrophage number were measured. Circulating sex hormone levels were correlated to WAT IL10 expression in 22 individuals and sex hormone effects on macrophage IL10 expression were investigated in vitro. RESULTS Obese women with T2D showed increased IL10 expression/secretion and IL-10-secreting WAT macrophage number compared to other female groups. This difference was absent in men. Non-obese women and men with T2D showed similar IL-10 levels compared to healthy controls, indicating that T2D alone does not regulate IL-10. Although WAT IL10 expression correlated with serum estrone (E1) concentrations, recombinant E1 did not affect macrophage IL10 expression in vitro. CONCLUSION WAT IL-10 levels are higher in women with obesity and T2D, but not in men and this effect is primarily attributed to obesity per se. This is less likely to be driven by circulating sex hormones. We propose that the WAT IL-10 might exert protective effects in obesity-associated chronic inflammation in women which could be one of the contributing factors for the decreased morbidity observed in women during obesity than men.
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Affiliation(s)
- Narmadha Subramanian
- Lipid laboratory, Unit of Endocrinology, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
- *Correspondence: Narmadha Subramanian, ; Jurga Laurencikiene,
| | - Beatriz Tavira
- Lipid laboratory, Unit of Endocrinology, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Kaisa Hofwimmer
- Lipid laboratory, Unit of Endocrinology, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Beate Gutsmann
- Medical Department III – Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany
| | - Lucas Massier
- Lipid laboratory, Unit of Endocrinology, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
- Medical Department III – Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany
| | - Julie Abildgaard
- Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
- Danish Diabetes Academy, Odense University Hospital, Odense, Denmark
| | - Anders Juul
- Department of Growth and Reproduction, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Mikael Rydén
- Lipid laboratory, Unit of Endocrinology, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Peter Arner
- Lipid laboratory, Unit of Endocrinology, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Jurga Laurencikiene
- Lipid laboratory, Unit of Endocrinology, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
- *Correspondence: Narmadha Subramanian, ; Jurga Laurencikiene,
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Sacilotto LB, Papini SJ, Mendes AL, Gatto M, Pereira PCM, Corrente JE, da Silva JDF. Relationship Between Lipodystrophy, Body Composition, Metabolic Profile, and Serum Levels of Adipocytokines. Front Nutr 2021; 8:750721. [PMID: 34957175 PMCID: PMC8698133 DOI: 10.3389/fnut.2021.750721] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Accepted: 11/05/2021] [Indexed: 11/13/2022] Open
Abstract
Background: Despite the benefits in improving the clinical state of people living with HIV/aids (PLWHA), some side effects associated with the use of antiretroviral therapy (ART) are reported. Redistribution of body fat has been associated with treatment and is characterized by morphological changes, also known as lipodystrophy. The complications of metabolic and morphological changes in these individuals seem to increase the risk of cardiovascular disease. Adipocytokines are proteins that have essential functions in biological processes, in which the levels of these proteins are related to the pathogenesis of metabolic syndrome (MS) and cardiovascular disease. Recent studies have shown that such levels are generally modified in PLWHA, regardless of whether the treatment is established or not. An application of methods for body fat estimation in patients with fat redistribution, as in the case of aids, especially those that quantify body fat by segments, appears to clarify these alterations and plays an important role in the development of multiprofessional treatment. Objectives: This investigation was carried out to compare and correlate body composition, biochemical metabolic parameters, and levels of adipocytokines and cytokines of PLWHA, with and without lipodystrophy, with individuals with negative HIV serology and stratified by sex. Material and Methods: This is a cross-sectional study in which body composition, metabolic and anthropometric changes, and levels of adipocytokines of 110 individuals were assessed. These individuals were paired in sex, age, and body mass index (BMI) and subdivided into three groups: PLWHA with and without a clinical diagnosis of lipodystrophy associated with HIV, and a group control. Results: Collinearity was identified both in the general sample and for genders of the waist-to-height ratio (WHtR) with all anthropometric parameters, except for muscle mass. The results show strong association between IFN-γ and TNF-α both in the general sample and for genders and moderate correlation between leptin and fasting glucose for women; worsening of the triglyceride profile in both women with lipodystrophy compared with the control group and men without lipodystrophy compared with the control group; higher serum TNF-α values among men without lipodystrophy compared to those with HIV-associated lipodystrophy (HALS). Conclusions: The results of this study underline that, considering the manifestations of the syndrome, these patients have a high-risk endocrine metabolic profile for cardiovascular events.
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Affiliation(s)
- Lívia Bertazzo Sacilotto
- Department of Infectology, Dermatology, Diagnostic Imaging, and Radiotherapy, Botucatu Medical School, São Paulo State University (UNESP), São Paulo, Brazil
| | - Silvia Justina Papini
- Department of Nursing, Botucatu Medical School, São Paulo State University (UNESP), São Paulo, Brazil
| | - Adriana Lucia Mendes
- Internal Medicine Department, Botucatu Medical School, São Paulo State University (UNESP), São Paulo, Brazil
| | - Mariana Gatto
- Internal Medicine Department, Botucatu Medical School, São Paulo State University (UNESP), São Paulo, Brazil
| | - Paulo Câmara Marques Pereira
- Department of Infectology, Dermatology, Diagnostic Imaging, and Radiotherapy, Botucatu Medical School, São Paulo State University (UNESP), São Paulo, Brazil
| | - José Eduardo Corrente
- Department of Biostatistics, Institute of Biosciences, São Paulo State University (UNESP), São Paulo, Brazil
| | - Julhiany de Fátima da Silva
- Department of Infectology, Dermatology, Diagnostic Imaging, and Radiotherapy, Botucatu Medical School, São Paulo State University (UNESP), São Paulo, Brazil
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Das B, Das M, Kalita A, Baro MR. The role of Wnt pathway in obesity induced inflammation and diabetes: a review. J Diabetes Metab Disord 2021; 20:1871-1882. [PMID: 34900830 PMCID: PMC8630176 DOI: 10.1007/s40200-021-00862-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 07/17/2021] [Indexed: 02/06/2023]
Abstract
Diabetes has become a major killer worldwide and at present, millions are affected by it. Being a chronic disease it increases the risk of other diseases ranging from pulmonary disorders to soft tissue infections. The loss of insulin-producing capacity of the pancreatic β-cells is the main reason for the development of the disease. Obesity is a major complication that can give rise to several other diseases such as cancer, diabetes, etc. Visceral adiposity is one of the major factors that play a role in the development of insulin resistance. Obesity causes a chronic low-grade inflammation in the tissues that further increases the chances of developing diabetes. Several pathways have been associated with the development of diabetes due to inflammation caused by obesity. The Wnt pathway is one such candidate pathway that is found to have a controlling effect on the development of insulin resistance. Moreover, the pathway has also been linked to obesity and inflammation. This review aims to find a connection between obesity, inflammation, and diabetes by taking the wnt pathway as the connecting link.
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Affiliation(s)
- Bhabajyoti Das
- Department of Zoology, Animal Physiology and Biochemistry Laboratory, Gauhati University, Guwahati, 781014 Assam India
| | - Manas Das
- Department of Zoology, Animal Physiology and Biochemistry Laboratory, Gauhati University, Guwahati, 781014 Assam India
| | - Anuradha Kalita
- Department of Zoology, Animal Physiology and Biochemistry Laboratory, Gauhati University, Guwahati, 781014 Assam India
| | - Momita Rani Baro
- Department of Zoology, Animal Physiology and Biochemistry Laboratory, Gauhati University, Guwahati, 781014 Assam India
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20
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Siddiqui A, Totonchian A, Jabar Ali JB, Ahmad I, Kumar J, Shiwlani S, Haroon DM, Makheja N, Rizwan A. Risk Factors Associated With Non-Respondence to Methotrexate in Rheumatoid Arthritis Patients. Cureus 2021; 13:e18112. [PMID: 34692323 PMCID: PMC8527277 DOI: 10.7759/cureus.18112] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/19/2021] [Indexed: 11/06/2022] Open
Abstract
Introduction: Oral methotrexate (MTX) is the first-line therapy for patients with rheumatoid arthritis (RA). However, not all RA patients respond to MTX. In this study, we will determine the risk factors associated with MTX failure. Methods: This retrospective study was conducted in tertiary care hospital in Pakistan. Data of 612 patients who were diagnosed with RA from June 2019 to January 2021 were retrieved from the medical record room. After inclusion, patients were divided into two groups; respondent and non-respondent. Their characteristics and demographics were compared. Results: Out of the total 612 patients, 112 (18.3%) were labelled as non-respondent to MTX. Non-respondents had a higher predominance of females (86.6% vs. 60.2%; p-value: 0.001), participants with body mass index (BMI) >25 kg/m2 (54.4% vs. 22.4%; p-value: <0.00001), smokers (34.8% vs. 18.2%; p-value: 0.0001), participants with diabetes (47.3% vs. 23.4%; p-value: <0.0001) and rheumatoid factor positivity (91.0% vs. 64.8%; p-value: <0.0001). Conclusion: Female gender, higher BMI, smoking, higher disease activity, and diabetes were associated with MTX failure. These easily available parameters can help predict the disease process and outcome of treatment. It is important to screen patients who are at risk of MTX failure, so a contingent treatment plan can be devised, in case patients do not respond to MTX.
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Affiliation(s)
- Aman Siddiqui
- Internal Medicine, Dow University of Health Sciences, Civil Hospital Karachi, Karachi, PAK
| | - Ali Totonchian
- Internal Medicine, Dow University of Health Sciences, Dow International Medical College, Karachi, PAK
| | - Jamila Begum Jabar Ali
- Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | - Ishtiaq Ahmad
- Internal Medicine, Khyber Medical College, Peshawar, PAK
| | - Jai Kumar
- Internal Medicine, Liaquat University of Medical and Health Sciences, Jamshoro, PAK
| | | | | | - Neeraj Makheja
- Internal Medicine, Ghulam Muhammad Mahar Medical College, Karachi, PAK
| | - Amber Rizwan
- Family Medicine, Jinnah Post Graduate Medical Center, Karachi, PAK
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21
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Kim JS, Galvão DA, Newton RU, Gray E, Taaffe DR. Exercise-induced myokines and their effect on prostate cancer. Nat Rev Urol 2021; 18:519-542. [PMID: 34158658 DOI: 10.1038/s41585-021-00476-y] [Citation(s) in RCA: 66] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/04/2021] [Indexed: 02/06/2023]
Abstract
Exercise is recognized by clinicians in the field of clinical oncology for its potential role in reducing the risk of certain cancers and in reducing the risk of disease recurrence and progression; yet, the underlying mechanisms behind this reduction in risk are not fully understood. Studies applying post-exercise blood serum directly to various types of cancer cell lines provide insight that exercise might have a role in inhibiting cancer growth via altered soluble and cell-free blood contents. Myokines, which are cytokines produced by muscle and secreted into the bloodstream, might offer multiple benefits to cellular metabolism (such as a reduction in insulin resistance, improved glucose uptake and reduced adiposity), and blood myokine levels can be altered with exercise. Alterations in the levels of myokines such as IL-6, IL-15, IL-10, irisin, secreted protein acidic risk in cysteine (SPARC), myostatin, oncostatin M and decorin might exert a direct inhibitory effect on cancer growth via inhibiting proliferation, promoting apoptosis, inducing cell-cycle arrest and inhibiting the epithermal transition to mesenchymal cells. The association of insulin resistance, hyperinsulinaemia and hyperlipidaemia with obesity can create a tumour-favourable environment; exercise-induced myokines can manipulate this environment by regulating adipose tissue and adipocytes. Exercise-induced myokines also have a critical role in increasing cytotoxicity and the infiltration of immune cells into the tumour.
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Affiliation(s)
- Jin-Soo Kim
- Exercise Medicine Research Institute, Edith Cowan University, Joondalup, WA, Australia.,School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia
| | - Daniel A Galvão
- Exercise Medicine Research Institute, Edith Cowan University, Joondalup, WA, Australia. .,School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
| | - Robert U Newton
- Exercise Medicine Research Institute, Edith Cowan University, Joondalup, WA, Australia.,School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia
| | - Elin Gray
- School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia
| | - Dennis R Taaffe
- Exercise Medicine Research Institute, Edith Cowan University, Joondalup, WA, Australia.,School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia
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22
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Kotikalapudi N, Sampath SJP, Sukesh Narayan S, R B, Nemani H, Mungamuri SK, Venkatesan V. The promise(s) of mesenchymal stem cell therapy in averting preclinical diabetes: lessons from in vivo and in vitro model systems. Sci Rep 2021; 11:16983. [PMID: 34417511 PMCID: PMC8379204 DOI: 10.1038/s41598-021-96121-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Accepted: 08/04/2021] [Indexed: 12/12/2022] Open
Abstract
Obesity (Ob) poses a significant risk factor for the onset of metabolic syndrome with associated complications, wherein the Mesenchymal Stem Cell (MSC) therapy shows pre-clinical success. Here, we explore the therapeutic applications of human Placental MSCs (P-MSCs) to address Ob-associated Insulin Resistance (IR) and its complications. In the present study, we show that intramuscular injection of P-MSCs homed more towards the visceral site, restored HOMA-IR and glucose homeostasis in the WNIN/GR-Ob (Ob-T2D) rats. P-MSC therapy was effective in re-establishing the dysregulated cytokines. We report that the P-MSCs activates PI3K-Akt signaling and regulates the Glut4-dependant glucose uptake and its utilization in WNIN/GR-Ob (Ob-T2D) rats compared to its control. Our data reinstates P-MSC treatment's potent application to alleviate IR and restores peripheral blood glucose clearance evidenced in stromal vascular fraction (SVF) derived from white adipose tissue (WAT) of the WNIN/GR-Ob rats. Gaining insights, we show the activation of the PI3K-Akt pathway by P-MSCs both in vivo and in vitro (palmitate primed 3T3-L1 cells) to restore the insulin sensitivity dysregulated adipocytes. Our findings suggest a potent application of P-MSCs in pre-clinical/Ob-T2D management.
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Affiliation(s)
- Nagasuryaprasad Kotikalapudi
- Division of Cell and Molecular Biology, ICMR-National Institute of Nutrition, Jamai-Osmania P.O., Tarnaka, Hyderabad, 500007, India
| | - Samuel Joshua Pragasam Sampath
- Division of Cell and Molecular Biology, ICMR-National Institute of Nutrition, Jamai-Osmania P.O., Tarnaka, Hyderabad, 500007, India
| | - Sinha Sukesh Narayan
- Division of Food Safety, ICMR-National Institute of Nutrition, Jamai-Osmania P.O., Tarnaka, Hyderabad, 500007, India
| | - Bhonde R
- Department of Regenerative Medicine, Manipal Institute of Regenerative Medicine, GKVK Post, Bellary Road, Allalasandra, Yelahanka, Bangalore, 560065, India
- Dr. D. Y. Patil Vidyapeeth, Pune, 411018, India
| | - Harishankar Nemani
- Division of Animal Facility, ICMR-National Institute of Nutrition, Jamai-Osmania P.O., Tarnaka, Hyderabad, 500007, India
| | - Sathish Kumar Mungamuri
- Division of Food Safety, ICMR-National Institute of Nutrition, Jamai-Osmania P.O., Tarnaka, Hyderabad, 500007, India
| | - Vijayalakshmi Venkatesan
- Division of Cell and Molecular Biology, ICMR-National Institute of Nutrition, Jamai-Osmania P.O., Tarnaka, Hyderabad, 500007, India.
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23
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Acharya KD, Noh HL, Graham ME, Suk S, Friedline RH, Gomez CC, Parakoyi AER, Chen J, Kim JK, Tetel MJ. Distinct Changes in Gut Microbiota Are Associated with Estradiol-Mediated Protection from Diet-Induced Obesity in Female Mice. Metabolites 2021; 11:metabo11080499. [PMID: 34436440 PMCID: PMC8398128 DOI: 10.3390/metabo11080499] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Revised: 07/24/2021] [Accepted: 07/27/2021] [Indexed: 01/14/2023] Open
Abstract
A decrease in ovarian estrogens in postmenopausal women increases the risk of weight gain, cardiovascular disease, type 2 diabetes, and chronic inflammation. While it is known that gut microbiota regulates energy homeostasis, it is unclear if gut microbiota is associated with estradiol regulation of metabolism. In this study, we tested if estradiol-mediated protection from high-fat diet (HFD)-induced obesity and metabolic changes are associated with longitudinal alterations in gut microbiota in female mice. Ovariectomized adult mice with vehicle or estradiol (E2) implants were fed chow for two weeks and HFD for four weeks. As reported previously, E2 increased energy expenditure, physical activity, insulin sensitivity, and whole-body glucose turnover. Interestingly, E2 decreased the tight junction protein occludin, suggesting E2 affects gut epithelial integrity. Moreover, E2 increased Akkermansia and decreased Erysipleotrichaceae and Streptococcaceae. Furthermore, Coprobacillus and Lactococcus were positively correlated, while Akkermansia was negatively correlated, with body weight and fat mass. These results suggest that changes in gut epithelial barrier and specific gut microbiota contribute to E2-mediated protection against diet-induced obesity and metabolic dysregulation. These findings provide support for the gut microbiota as a therapeutic target for treating estrogen-dependent metabolic disorders in women.
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Affiliation(s)
- Kalpana D. Acharya
- Neuroscience Department, Wellesley College, Wellesley, MA 02481, USA; (K.D.A.); (M.E.G.); (C.C.G.); (A.E.R.P.)
| | - Hye L. Noh
- Program in Molecular Medicine, Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA; (H.L.N.); (S.S.); (R.H.F.); (J.K.K.)
| | - Madeline E. Graham
- Neuroscience Department, Wellesley College, Wellesley, MA 02481, USA; (K.D.A.); (M.E.G.); (C.C.G.); (A.E.R.P.)
| | - Sujin Suk
- Program in Molecular Medicine, Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA; (H.L.N.); (S.S.); (R.H.F.); (J.K.K.)
| | - Randall H. Friedline
- Program in Molecular Medicine, Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA; (H.L.N.); (S.S.); (R.H.F.); (J.K.K.)
| | - Cesiah C. Gomez
- Neuroscience Department, Wellesley College, Wellesley, MA 02481, USA; (K.D.A.); (M.E.G.); (C.C.G.); (A.E.R.P.)
| | - Abigail E. R. Parakoyi
- Neuroscience Department, Wellesley College, Wellesley, MA 02481, USA; (K.D.A.); (M.E.G.); (C.C.G.); (A.E.R.P.)
| | - Jun Chen
- Department of Health Sciences Research & Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA;
| | - Jason K. Kim
- Program in Molecular Medicine, Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA; (H.L.N.); (S.S.); (R.H.F.); (J.K.K.)
| | - Marc J. Tetel
- Neuroscience Department, Wellesley College, Wellesley, MA 02481, USA; (K.D.A.); (M.E.G.); (C.C.G.); (A.E.R.P.)
- Correspondence:
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24
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Kuiper-Makris C, Selle J, Nüsken E, Dötsch J, Alejandre Alcazar MA. Perinatal Nutritional and Metabolic Pathways: Early Origins of Chronic Lung Diseases. Front Med (Lausanne) 2021; 8:667315. [PMID: 34211985 PMCID: PMC8239134 DOI: 10.3389/fmed.2021.667315] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Accepted: 05/12/2021] [Indexed: 12/12/2022] Open
Abstract
Lung development is not completed at birth, but expands beyond infancy, rendering the lung highly susceptible to injury. Exposure to various influences during a critical window of organ growth can interfere with the finely-tuned process of development and induce pathological processes with aberrant alveolarization and long-term structural and functional sequelae. This concept of developmental origins of chronic disease has been coined as perinatal programming. Some adverse perinatal factors, including prematurity along with respiratory support, are well-recognized to induce bronchopulmonary dysplasia (BPD), a neonatal chronic lung disease that is characterized by arrest of alveolar and microvascular formation as well as lung matrix remodeling. While the pathogenesis of various experimental models focus on oxygen toxicity, mechanical ventilation and inflammation, the role of nutrition before and after birth remain poorly investigated. There is accumulating clinical and experimental evidence that intrauterine growth restriction (IUGR) as a consequence of limited nutritive supply due to placental insufficiency or maternal malnutrition is a major risk factor for BPD and impaired lung function later in life. In contrast, a surplus of nutrition with perinatal maternal obesity, accelerated postnatal weight gain and early childhood obesity is associated with wheezing and adverse clinical course of chronic lung diseases, such as asthma. While the link between perinatal nutrition and lung health has been described, the underlying mechanisms remain poorly understood. There are initial data showing that inflammatory and nutrient sensing processes are involved in programming of alveolarization, pulmonary angiogenesis, and composition of extracellular matrix. Here, we provide a comprehensive overview of the current knowledge regarding the impact of perinatal metabolism and nutrition on the lung and beyond the cardiopulmonary system as well as possible mechanisms determining the individual susceptibility to CLD early in life. We aim to emphasize the importance of unraveling the mechanisms of perinatal metabolic programming to develop novel preventive and therapeutic avenues.
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Affiliation(s)
- Celien Kuiper-Makris
- Department of Pediatric and Adolescent Medicine, Translational Experimental Pediatrics—Experimental Pulmonology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Jaco Selle
- Department of Pediatric and Adolescent Medicine, Translational Experimental Pediatrics—Experimental Pulmonology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Eva Nüsken
- Department of Pediatric and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Jörg Dötsch
- Department of Pediatric and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Miguel A. Alejandre Alcazar
- Department of Pediatric and Adolescent Medicine, Translational Experimental Pediatrics—Experimental Pulmonology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Excellence Cluster on Stress Responses in Aging-associated Diseases (CECAD), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- Member of the German Centre for Lung Research (DZL), Institute for Lung Health, University of Giessen and Marburg Lung Centre (UGMLC), Gießen, Germany
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25
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Chen Q, Wang B, Wang S, Qian X, Li X, Zhao J, Zhang H, Chen W, Wang G. Modulation of the Gut Microbiota Structure with Probiotics and Isoflavone Alleviates Metabolic Disorder in Ovariectomized Mice. Nutrients 2021; 13:1793. [PMID: 34070274 PMCID: PMC8225012 DOI: 10.3390/nu13061793] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 05/12/2021] [Accepted: 05/21/2021] [Indexed: 02/06/2023] Open
Abstract
The decrease in ovarian hormone secretion that occurs during menopause results in an increase in body weight and adipose tissue mass. Probiotics and soy isoflavones (SIFs) could affect the gut microbiota and exert anti-obesity effects. The objective of this study was to investigate the effects of probiotics and a diet containing SIF (SIF diet) on ovariectomized mice with menopausal obesity, including the gut microbiome. The results demonstrate that Bifidobacterium longum 15M1 can reverse menopausal obesity, whilst the combination of Lactobacillus plantarum 30M5 and a SIF diet was more effective in alleviating menopausal lipid metabolism disorder than either components alone. Probiotics and SIFs play different anti-obesity roles in menopausal mice. Furthermore, 30M5 alters the metabolites of the gut microbiota that increase the circulating estrogen level, upregulates the expression of estrogen receptor α in abdominal adipose tissue and improves the production of short-chain fatty acids (SCFAs). A SIF diet can significantly alter the structure of the fecal bacterial community and enrich the pathways related to SCFAs production. Moreover, 30M5 and a SIF diet acted synergistically to effectively resolve abnormal serum lipid levels in ovariectomized mice, and these effects appear to be associated with regulation of the diversity and structure of the intestinal microbiota to enhance SCFAs production and promote estrogen circulation.
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Affiliation(s)
- Qian Chen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (Q.C.); (B.W.); (S.W.); (X.Q.); (X.L.); (J.Z.); (H.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Botao Wang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (Q.C.); (B.W.); (S.W.); (X.Q.); (X.L.); (J.Z.); (H.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Shunhe Wang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (Q.C.); (B.W.); (S.W.); (X.Q.); (X.L.); (J.Z.); (H.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Xin Qian
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (Q.C.); (B.W.); (S.W.); (X.Q.); (X.L.); (J.Z.); (H.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Xiu Li
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (Q.C.); (B.W.); (S.W.); (X.Q.); (X.L.); (J.Z.); (H.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Jianxin Zhao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (Q.C.); (B.W.); (S.W.); (X.Q.); (X.L.); (J.Z.); (H.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- International Joint Research Laboratory for Probiotics, Jiangnan University, Wuxi 214122, China
- (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China
| | - Hao Zhang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (Q.C.); (B.W.); (S.W.); (X.Q.); (X.L.); (J.Z.); (H.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
- Wuxi Translational Medicine Research Center and Jiangsu Translational Medicine Research Institute Wuxi Branch, Wuxi 214122, China
| | - Wei Chen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (Q.C.); (B.W.); (S.W.); (X.Q.); (X.L.); (J.Z.); (H.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
| | - Gang Wang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (Q.C.); (B.W.); (S.W.); (X.Q.); (X.L.); (J.Z.); (H.Z.); (W.C.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- International Joint Research Laboratory for Probiotics, Jiangnan University, Wuxi 214122, China
- (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China
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26
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Darakjian L, Deodhar M, Turgeon J, Michaud V. Chronic Inflammatory Status Observed in Patients with Type 2 Diabetes Induces Modulation of Cytochrome P450 Expression and Activity. Int J Mol Sci 2021; 22:ijms22094967. [PMID: 34067027 PMCID: PMC8124164 DOI: 10.3390/ijms22094967] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 04/30/2021] [Accepted: 05/05/2021] [Indexed: 02/07/2023] Open
Abstract
Diabetes mellitus is a metabolic disease that causes a hyperglycemic status which leads, over time, to serious damage to the heart, blood vessels, eyes, kidneys and nerves. The most frequent form of diabetes is type 2 diabetes mellitus (T2DM) which is often part of a metabolic syndrome (hyperglycaemia, hypertension, hypercholesterolemia, abdominal obesity) that usually requires the use of several medications from different drug classes to bring each of these conditions under control. T2DM is associated with an increase in inflammatory markers such as interleukin-6 (IL-6) and the tumor necrosis factor alpha (TNF-α). Higher levels of IL-6 and TNF-α are associated with a downregulation of several drug metabolizing enzymes, especially the cytochrome P450 (P450) isoforms CYP3As and CYP2C19. A decrease in these P450 isoenzymes may lead to unexpected rise in plasma levels of substrates of these enzymes. It could also give rise to a mismatch between the genotypes determined for these enzymes, the predicted phenotypes based on these genotypes and the phenotypes observed clinically. This phenomenon is described as phenoconversion. Phenoconversion typically results from either a disease (such as T2DM) or concomitant administration of medications inducing or inhibiting (including competitive or non-competitive inhibition) a P450 isoenzyme used by other substrates for their elimination. Phenoconversion could have a significant impact on drug effects and genotypic-focused clinical outcomes. As the aging population is exposed to polypharmacy along with inflammatory comorbidities, consideration of phenoconversion related to drug metabolizing enzymes is of importance when applying pharmacogenomic results and establishing personalized and more precise drug regimens.
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Affiliation(s)
- Lucy Darakjian
- Tabula Rasa HealthCare, Precision Pharmacotherapy Research and Development Institute, Orlando, FL 32827, USA; (L.D.); (M.D.); (J.T.)
| | - Malavika Deodhar
- Tabula Rasa HealthCare, Precision Pharmacotherapy Research and Development Institute, Orlando, FL 32827, USA; (L.D.); (M.D.); (J.T.)
| | - Jacques Turgeon
- Tabula Rasa HealthCare, Precision Pharmacotherapy Research and Development Institute, Orlando, FL 32827, USA; (L.D.); (M.D.); (J.T.)
- Faculty of Pharmacy, Université de Montréal, Montreal, QC H3C 3J7, Canada
| | - Veronique Michaud
- Tabula Rasa HealthCare, Precision Pharmacotherapy Research and Development Institute, Orlando, FL 32827, USA; (L.D.); (M.D.); (J.T.)
- Faculty of Pharmacy, Université de Montréal, Montreal, QC H3C 3J7, Canada
- Correspondence: ; Tel.: +1-407-454-9964
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27
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Atakan MM, Koşar ŞN, Güzel Y, Tin HT, Yan X. The Role of Exercise, Diet, and Cytokines in Preventing Obesity and Improving Adipose Tissue. Nutrients 2021; 13:nu13051459. [PMID: 33922998 PMCID: PMC8145589 DOI: 10.3390/nu13051459] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 04/20/2021] [Accepted: 04/22/2021] [Indexed: 12/17/2022] Open
Abstract
The prevalence of obesity continues to rise worldwide despite evidence-based public health recommendations. The promise to adopt a healthy lifestyle is increasingly important for tackling this global epidemic. Calorie restriction or regular exercise or a combination of the two is accepted as an effective strategy in preventing or treating obesity. Furthermore, the benefits conferred by regular exercise to overcome obesity are attributed not only to reduced adiposity or reduced levels of circulating lipids but also to the proteins, peptides, enzymes, and metabolites that are released from contracting skeletal muscle or other organs. The secretion of these molecules called cytokines in response to exercise induces browning of white adipose tissue by increasing the expression of brown adipocyte-specific genes within the white adipose tissue, suggesting that exercise-induced cytokines may play a significant role in preventing obesity. In this review, we present research-based evidence supporting the effects of exercise and various diet interventions on preventing obesity and adipose tissue health. We also discuss the interplay between adipose tissue and the cytokines secreted from skeletal muscle and other organs that are known to affect adipose tissue and metabolism.
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Affiliation(s)
- Muhammed Mustafa Atakan
- Division of Exercise Nutrition and Metabolism, Faculty of Sport Sciences, Hacettepe University, 06800 Ankara, Turkey; (M.M.A.); (Ş.N.K.); (Y.G.)
| | - Şükran Nazan Koşar
- Division of Exercise Nutrition and Metabolism, Faculty of Sport Sciences, Hacettepe University, 06800 Ankara, Turkey; (M.M.A.); (Ş.N.K.); (Y.G.)
| | - Yasemin Güzel
- Division of Exercise Nutrition and Metabolism, Faculty of Sport Sciences, Hacettepe University, 06800 Ankara, Turkey; (M.M.A.); (Ş.N.K.); (Y.G.)
| | - Hiu Tung Tin
- Institute for Health and Sport (iHeS), Victoria University, P.O. Box 14428, Melbourne 8001, Australia;
| | - Xu Yan
- Institute for Health and Sport (iHeS), Victoria University, P.O. Box 14428, Melbourne 8001, Australia;
- Sarcopenia Research Program, Australia Institute for Musculoskeletal Sciences (AIMSS), Melbourne 3021, Australia
- Correspondence: ; Tel.: +61-3-9919-4024; Fax: +61-3-9919-5615
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28
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Anche P, Maiya GA, Kamath SU, Shastry BA. Influence of a 12-week physical activity program on leptin resistance in metabolic syndrome: a preliminary study. Int J Diabetes Dev Ctries 2021. [DOI: 10.1007/s13410-021-00928-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Abstract
Purpose
Metabolic syndrome is a condition with clustering of risk factors like insulin resistance, obesity, dyslipidemia, and hypertension. Leptin is a protein of obese gene produced by white adipose tissue. Leptin resistance is the insensitivity of leptin in hypothalamus despite high amounts in blood causing obesity and metabolic syndrome. The study focused on the influence of a 12-week physical activity promotion program on leptin resistance in people with metabolic syndrome
Methods
After approval from institutional ethics committee (IEC 343-2018), 18 participants (males N= 4, females N=14) of age group 45.0±7.6 years with metabolic syndrome according to (NCEP ATP-III) criteria were included in the study. The participants underwent a 12-week physical activity program consisting of 150 min of moderate to vigorous activity per week as per GPAQ domains—work, transport, and recreation. The outcomes were measured at baseline and after 12 weeks.
Results
Out of 18 participants, 10 participants who completed the study were analysed. Twelve-week physical activity showed significant changes in waist circumference (p=0.047), post prandial blood glucose (p=0.0396), triglycerides (p=0.0323), body mass index (p=0.0056), subcutaneous fat (p=0.0354), and basal metabolic rate (p=0.0035). Fasting blood glucose (p=0.254), lipid profiles (total cholesterol (p=0.062)), high-density lipoprotein (p=0.367), low-density lipoprotein (p=0.641), and leptin showed insignificant change (p=0.328). Global physical activity questionnaire showed significant change (p=0.0254) suggesting changes in physical activity behaviors.
Conclusion
From present study, it is concluded that a 12-week physical activity promotion program brought marginal changes in leptin levels and has potential to modify metabolic syndrome parameters and improve physical activity.
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Fahmy A, Abdeldaiem H, Abdelsattar M, Aboyoussif T, Assem A, Zahran A, Elgebaly O. Impact of Bariatric Surgery on Sexual Dysfunction in Obese Men. Sex Med 2021; 9:100322. [PMID: 33592350 PMCID: PMC8072175 DOI: 10.1016/j.esxm.2021.100322] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 01/03/2021] [Accepted: 01/04/2021] [Indexed: 11/29/2022] Open
Abstract
Introduction Currently bariatric surgery is the most effective treatment for significant and sustained weight loss. Erectile and endothelial dysfunctions may share some metabolic and vascular pathways in common that may be influenced by weight loss. Aim The aim of the study was to assess the impact of surgically induced weight loss on the erectile function on obese patients undergoing laparoscopic sleeve gastrectomy (LSG). We also aimed to examine the proposed underlying mechanism associated with improvement in erectile function after weight loss by LSG. Methods Eighty-two consecutive obese men who underwent a LGS were followed up for 12 months. All operations were performed by the same surgeon at a single institution. Main Outcome measure Patients were examined both before and after 12 months of LSG for biochemical tests; total serum cholesterol, triglyceride, C-reactive protein, interleukin-6, and endothelial nitric oxide synthase, and for erectile function tests. International Index of Erectile Function (IIEF) scores were recorded. Results Eighty-two men (mean age 39 ± 14.6 years, range 24–62; mean BMI 41.2 ± 4.8 kg/m2) completed all preoperative and postoperative questionnaires and biochemical tests. At 12 months, the mean weight loss was 34.8 kg and the mean BMI decrease was 8.6 kg/m2. Preoperative and postoperative IIEF scores of the 65 sexually active patients showed significant improvement in erectile function (21.2 ± 5.7 vs 26.5 ± 4.5; P = .02). Seventeen (20.7%) men were not sexually active preoperatively; only 5 became sexually active postoperatively. Men had a significant decrease in serum cholesterol and triglyceride levels. Nitric oxide synthase activity showed a significant increase (P < .02). In addition, our patients showed a statistically significant decrease in interleukin-6 levels and C-reactive protein compared with preoperative period (P < .03 and P < .01, respectively). Conclusion A significant improvement of erectile function was documented among obese young men undergoing LGS. This improvement was documented both clinically by improvement in IIEF score postoperatively and biochemically. A Fahmy, H Abdeldaiem, M Abdelsattar, et al. Impact of Bariatric Surgery on Sexual Dysfunction in Obese Men. Sex Med 2021;9:100322.
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Affiliation(s)
- Ahmed Fahmy
- Department of Urology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Hussien Abdeldaiem
- Department of Urology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Mohamed Abdelsattar
- Department of Urology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Tamer Aboyoussif
- Department of Urology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Akram Assem
- Department of Urology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Abdelrahman Zahran
- Department of Urology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Omar Elgebaly
- Department of Urology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
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IL-6 Reduces Mitochondrial Replication, and IL-6 Receptors Reduce Chronic Inflammation in NAFLD and Type 2 Diabetes. Int J Mol Sci 2021; 22:ijms22041774. [PMID: 33579000 PMCID: PMC7916777 DOI: 10.3390/ijms22041774] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 02/04/2021] [Accepted: 02/08/2021] [Indexed: 12/15/2022] Open
Abstract
Interleukin (IL)-6 family cytokines act through a receptor complex with gp130 subunits. IL-6 is a pleiotropic cytokine that regulates inflammation and liver regeneration. Mitochondria are the first to respond to stress and adapt their dynamics in conditions of damage. In this regard, the study aimed to investigate the role of the IL-6 cytokine family (sIL-6Ra, gp130/sIL-6Rb, and IL-11) in the regulation of mitochondrial dynamics in the liver in obese patients and to assess the contribution of these cytokines to the pathogenesis of type 2 diabetes mellitus (T2DM). We studied 134 obese patients with and without T2DM and 41 healthy donors. We found that increasing the concentration of sIL-6Ra and gp130/sIL-6Rb protected against carbohydrate disorders in obese patients and prevented non-alcoholic fatty liver disease (NAFLD) progression in obese patients. An increase in plasma IL-6 levels is associated with decreased, mitochondrial transcription factor A (TFAM) protein production in liver biopsies in obese patients with and without T2DM. Replication, transcription, and division processes in liver biopsy were reduced in patients with T2DM. Inflammatory processes stimulate liver cell apoptosis in obese patients with T2DM. The increase in IL-11 levels is associated with decreased pro-apoptotic Bcl-2-associated X protein (BAX) protein production in obese patients with and without T2DM.
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Niederseer D, Wernly B, Aigner E, Stickel F, Datz C. NAFLD and Cardiovascular Diseases: Epidemiological, Mechanistic and Therapeutic Considerations. J Clin Med 2021; 10:467. [PMID: 33530440 PMCID: PMC7865665 DOI: 10.3390/jcm10030467] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 01/21/2021] [Accepted: 01/21/2021] [Indexed: 02/06/2023] Open
Abstract
Overwhelming evidence suggests an association of cardiovascular disease (CVD) with non-alcoholic fatty liver disease (NAFLD); however, the underlying mechanisms remain largely speculative. It is, however, likely that common mechanisms contribute to the development of CVD and NAFLD, with lifestyle factors such as smoking, sedentary lifestyle with poor nutrition habits and physical inactivity being major candidates. These behavioral factors, on a predisposing genetic background, trigger changes in gut microbiota, inflammation, dyslipidemia and oxidative stress, leading to metabolic syndrome, diabetes and obesity as well as atherosclerosis. Treatment options to counteract both the progression and development of CVD and NAFLD include lifestyle interventions, optimal medical therapy of comorbid conditions and, as final possibility, bariatric surgery. As no causal pharmacotherapy of NAFLD is available, further research is urgently needed to address the unmet need of a growing population with NAFLD and CVD.
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Affiliation(s)
- David Niederseer
- Department of Cardiology, University Heart Center Zurich, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland;
| | - Bernhard Wernly
- Department of Anaesthesiology, Perioperative Medicine and Intensive Care Medicine, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria;
- Center for Public Health and Healthcare Research, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria
- Department of Cardiology, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria
| | - Elmar Aigner
- First Department of Medicine, Paracelsus Medical University, 5020 Salzburg, Austria;
| | - Felix Stickel
- Department of Gastroenterology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland;
| | - Christian Datz
- Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University, 5110 Oberndorf, Austria
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Prabhu S, Deng H, Cross TWL, Shahoei SH, Konopka CJ, Gonzalez Medina N, Applegate CC, Wallig MA, Dobrucki LW, Nelson ER, Smith AM, Swanson KS. Nanocarriers targeting adipose macrophages increase glucocorticoid anti-inflammatory potency to ameliorate metabolic dysfunction. Biomater Sci 2021; 9:506-518. [PMID: 33200765 DOI: 10.1039/d0bm01142h] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Obesity is associated with systemic inflammation due to macrophage accumulation in adipose tissue (AT). AT macrophages are, therefore, a target for therapeutics to modulate inflammation and prevent comorbidities. Because inflammatory processes have pleiotropic effects throughout the body and are intertwined with metabolic axes, systemic anti-inflammatory therapies are often harmful. We report that targeting AT macrophages using dextran nanocarriers radically alters the pharmacology of anti-inflammatory glucocorticoids, uncoupling the metabolic axis in obese mice. Following a single treatment, expression of inflammatory mediators and markers of inflammatory macrophages decreased with a nearly 20-fold higher potency compared with free drug. As a result, long-term treatment resulted in potent fat mobilization, AT reduction, weight loss, improved glucose tolerance, and altered AT gene expression profiles that led to elevated liver stress. Two weeks after treatment ceased, gene expression of inflammatory mediators in AT remained lower than obese controls, while gene expression related to metabolic function improved. These data demonstrate that nanocarriers show potential for amelioration of obesity-related AT inflammation and metabolic dysfunction, highlighting an important opportunity for nanomedicine to impact chronic metabolic disorders with complex and poorly understood etiology.
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Affiliation(s)
- Suma Prabhu
- Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
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Abstract
Non-Alcoholic Fatty Liver Disease (NAFLD) is caused by the accumulation of fat in over 5% of hepatocytes in the absence of alcohol consumption. NAFLD is considered the hepatic manifestation of metabolic syndrome (MS). Recently, an expert consensus suggested as more appropriate the term MAFLD (metabolic-associated fatty liver disease). Insulin resistance (IR) plays a key role in the development of NAFLD, as it causes an increase in hepatic lipogenesis and an inhibition of adipose tissue lipolysis. Beyond the imbalance of adipokine levels, the increase in the mass of visceral adipose tissue also determines an increase in free fatty acid (FFA) levels. In turn, an excess of FFA is able to determine IR through the inhibition of the post-receptor insulin signal. Adipocytes secrete chemokines, which are able to enroll macrophages inside the adipose tissue, responsible, in turn, for the increased levels of TNF-α. The latter, as well as resistin and other pro-inflammatory cytokines such as IL-6, enhances insulin resistance and correlates with endothelial dysfunction and an increased cardiovascular (CV) risk. In this review, the role of diet, intestinal microbiota, genetic and epigenetic factors, low-degree chronic systemic inflammation, mitochondrial dysfunction, and endoplasmic reticulum stress on NAFLD have been addressed. Finally, the clinical impact of NAFLD on cardiovascular and renal outcomes, and its direct link with type 2 diabetes have been discussed.
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Faraji S, Alizadeh M. Mechanistic Effects of Vitamin D Supplementation on Metabolic Syndrome Components in Patients with or without Vitamin D Deficiency. J Obes Metab Syndr 2020; 29:270-280. [PMID: 32747610 PMCID: PMC7789020 DOI: 10.7570/jomes20003] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 01/21/2020] [Accepted: 05/17/2020] [Indexed: 12/11/2022] Open
Abstract
The prevalences of metabolic syndrome (MetS) and vitamin D deficiency are increasing dramatically worldwide. MetS is a major challenge because it can increase the risk of most non-communicable diseases. The beneficial effect of vitamin D on MetS components remains controversial, so the present review focused on the clinical effects of vitamin D supplementation on MetS components. Vitamin D can inhibit the protein expression of nuclear factor beta; improve arterial stiffness; decrease renin-angiotensin-aldosterone system activity, parathyroid hormone levels, inflammatory cytokines, 3-hydroxy-3-methylglutaryl-coenzyme A reductase, and lanosterol 14 α-demethylase enzyme activity; increase the activity of lipoprotein lipase; alter gene expression in C2C12 cells; and improve phospholipid metabolism and mitochondrial oxidation. We tried to elucidate and analyze almost all evidence from randomized controlled trial studies of the efficacy of vitamin D supplementation in patients with MetS. The findings of the present study reported beneficial effects of vitamin D supplementation on mentioned factors. Vitamin D supplementation is recommended in people with vitamin D deficiency even if it has no considerable effect on most MetS factors. However, existing data from interventional studies are insufficient to reach a definitive conclusion about the effect of vitamin D supplementation on MetS components in patients without vitamin D deficiency. Thus, new clinical studies are needed to test the hypothesis that vitamin D supplementation could alleviate MetS components in patients with sufficient intake of vitamin D.
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Affiliation(s)
- Samira Faraji
- Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran.,Department of Nutrition, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Mohammad Alizadeh
- Department of Nutrition, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran.,Food and Beverages Safety Research Center, Urmia University of Medical Sciences, Urmia, Iran
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Annett S, Moore G, Robson T. Obesity and Cancer Metastasis: Molecular and Translational Perspectives. Cancers (Basel) 2020; 12:E3798. [PMID: 33339340 PMCID: PMC7766668 DOI: 10.3390/cancers12123798] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Revised: 12/11/2020] [Accepted: 12/14/2020] [Indexed: 02/06/2023] Open
Abstract
Obesity is a modern health problem that has reached pandemic proportions. It is an established risk factor for carcinogenesis, however, evidence for the contribution of adipose tissue to the metastatic behavior of tumors is also mounting. Over 90% of cancer mortality is attributed to metastasis and metastatic tumor cells must communicate with their microenvironment for survival. Many of the characteristics observed in obese adipose tissue strongly mirror the tumor microenvironment. Thus in the case of prostate, pancreatic and breast cancer and esophageal adenocarcinoma, which are all located in close anatomical proximity to an adipose tissue depot, the adjacent fat provides an ideal microenvironment to enhance tumor growth, progression and metastasis. Adipocytes provide adipokines, fatty acids and other soluble factors to tumor cells whilst immune cells infiltrate the tumor microenvironment. In addition, there are emerging studies on the role of the extracellular vesicles secreted from adipose tissue, and the extracellular matrix itself, as drivers of obesity-induced metastasis. In the present review, we discuss the major mechanisms responsible for the obesity-metastatic link. Furthermore, understanding these complex mechanisms will provide novel therapies to halt the tumor-adipose tissue crosstalk with the ultimate aim of inhibiting tumor progression and metastatic growth.
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Affiliation(s)
| | | | - Tracy Robson
- School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Science, 123 St Stephen’s Green, Dublin D02 YN77, Ireland; (S.A.); (G.M.)
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Purdy JC, Shatzel JJ. The hematologic consequences of obesity. Eur J Haematol 2020; 106:306-319. [PMID: 33270290 DOI: 10.1111/ejh.13560] [Citation(s) in RCA: 85] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 11/28/2020] [Accepted: 12/01/2020] [Indexed: 12/12/2022]
Abstract
The prevalence of obesity is increasing and progressively influencing physician-patient interactions. While there is a sizable amount of data demonstrating that obesity is a state of low-grade inflammation, to our knowledge, there is no single review summarizing its effects on hematologic parameters and thrombotic risk. We performed a literature search which largely surfaced observational studies, with a few systematic reviews and meta-analyses of these studies. We took care to review the mechanisms driving an inflammatory state and obesity's effect on white blood cells, red blood cells, platelets, and thrombotic risk. There is an observed relative, and sometimes absolute leukocytosis driven by this inflammatory state. Obesity is also associated with increased platelet counts and an increased risk for venous thromboembolism (VTE). Lastly, the association between obesity, iron deficiency (ID), and red blood cell counts may be present but remains uncertain. Recognizing the above associations may provide clinicians with reassurance regarding otherwise unexplained hematologic abnormalities in obese individuals. We hope this review will prompt future studies to further understand the underlying mechanisms driving these abnormalities and identify modifiable risk factors and potential therapeutic targets to prevent the development of probable obesity-associated conditions with significant morbidity and mortality, such as ID and VTE.
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Affiliation(s)
- Johanna C Purdy
- Division of General Internal Medicine and Geriatrics, Oregon Health & Science University, Portland, OR, USA
| | - Joseph J Shatzel
- Division of Hematology and Oncology, Oregon Health & Science University, Portland, OR, USA.,Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR, USA
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The Influence of Physical Activity on the Bioactive Lipids Metabolism in Obesity-Induced Muscle Insulin Resistance. Biomolecules 2020; 10:biom10121665. [PMID: 33322719 PMCID: PMC7764345 DOI: 10.3390/biom10121665] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 12/08/2020] [Accepted: 12/11/2020] [Indexed: 12/14/2022] Open
Abstract
High-fat diet consumption and lack of physical activity are important risk factors for metabolic disorders such as insulin resistance and cardiovascular diseases. Insulin resistance is a state of a weakened response of tissues such as skeletal muscle, adipose tissue, and liver to insulin, which causes an increase in blood glucose levels. This condition is the result of inhibition of the intracellular insulin signaling pathway. Skeletal muscle is an important insulin-sensitive tissue that accounts for about 80% of insulin-dependent glucose uptake. Although the exact mechanism by which insulin resistance is induced has not been thoroughly understood, it is known that insulin resistance is most commonly associated with obesity. Therefore, it is believed that lipids may play an important role in inducing insulin resistance. Among lipids, researchers’ attention is mainly focused on biologically active lipids: diacylglycerols (DAG) and ceramides. These lipids are able to regulate the activity of intracellular enzymes, including those involved in insulin signaling. Available data indicate that physical activity affects lipid metabolism and has a positive effect on insulin sensitivity in skeletal muscles. In this review, we have presented the current state of knowledge about the impact of physical activity on insulin resistance and metabolism of biologically active lipids.
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Effects of an Indoor Cycling Program on Cardiometabolic Factors in Women with Obesity vs. Normal Body Weight. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17238718. [PMID: 33255278 PMCID: PMC7727675 DOI: 10.3390/ijerph17238718] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/01/2020] [Accepted: 11/20/2020] [Indexed: 12/31/2022]
Abstract
The study aimed to provide evidence on the impact of indoor cycling (IC) in reducing cardiometabolic risk factors. The study compares the effects of a 3 month IC program involving three 55 min sessions per week on women aged 40–60 years, with obesity (OW, n = 18) vs. women with normal body weight (NW, n = 8). At baseline and at the end of the study, anthropometric parameters, oxygen uptake (VO2 peak), and serum parameters: glucose, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG), insulin, human anti-oxidized low-density lipoprotein antibody (OLAb), total blood antioxidant capacity (TAC), thiobarbituric acid reactive substances (TBARS), endothelial nitric oxide synthase (eNOS), C-reactive protein (CRP), lipid accumulation product (LAP), and homeostasis model assessment of insulin resistance index (HOMA IR) were determined. Before the intervention, VO2 peak and HDL-C levels were significantly lower and levels of TG, LAP, insulin, HOMA-IR, and CRP were significantly higher in the OW group compared to those in the NW group. After the intervention, only the OW group saw a decrease in body mass, total cholesterol, OLAb, TBARS, and CRP concentration and an increase in total body skeletal muscle mass and HDL-C concentration. In response to the IC training, measured indicators in the OW group were seen to approach the recommended values, but all between-group differences remained significant. Our results demonstrate that IC shows promise for reducing cardiometabolic risk factors, especially dyslipidemia. After 12 weeks of regular IC, the metabolic function of the OW group adapted in many aspects to be more like that of the NW group.
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Lubrano C, Risi R, Masi D, Gnessi L, Colao A. Is obesity the missing link between COVID-19 severity and air pollution? ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2020; 266:115327. [PMID: 32771867 PMCID: PMC7397942 DOI: 10.1016/j.envpol.2020.115327] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/24/2020] [Revised: 07/24/2020] [Accepted: 07/27/2020] [Indexed: 05/22/2023]
Abstract
In the previous publication "Can atmospheric pollution be considered a co-factor in extremely high level of SARS-CoV-2 lethality in Northern Italy?" Conticini et al. hypothesized that the surplus of lethality of the novel SARS-CoV-2 in Northern Italy may be at least in part explained by the evidence of highest pollution reported in this area, as both severe COVID-19 and smog exposure are correlated to an innate immune system hyper-activation with subsequent lung inflammation and injury. Since this hypothesis alone does not fully explain why specific subgroups of patients are at major risk, we hypothesized that obesity may be one of the links between COVID-19 severity and high level of air pollution. First, obesity is a predisposing factor for SARS-Cov-2 infection and worse COVID-19 outcomes, and unequivocal evidence demonstrated that fat mass excess is independently associated with several pulmonary diseases and lung inflammation. Moreover, it has been shown that obesity may intensify the detrimental effects of air pollution on the lungs, and this is not surprising if we consider that these conditions share an excessive activation of the immune system and a lung inflammatory infiltrate. Finally, fat mass excess has also been speculated to be itself a consequence of air pollutants exposure, which has been proved to induce metabolic disruption and weight gain in murine models. In conclusion, although many variables must be taken into account in the analysis of the pandemic, our observations suggest that obesity may act as effect modifier of smog-induced lung-injury, and the concomitant presence of these two factors could better explain the higher virulence, faster spread and greater mortality of SARS-CoV-2 in Northern Italy compared to the rest of the country.
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Affiliation(s)
- Carla Lubrano
- Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Viale Regina Elena, 324, 00161, Rome, Italy.
| | - Renata Risi
- Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Viale Regina Elena, 324, 00161, Rome, Italy
| | - Davide Masi
- Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Viale Regina Elena, 324, 00161, Rome, Italy
| | - Lucio Gnessi
- Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Viale Regina Elena, 324, 00161, Rome, Italy
| | - Annamaria Colao
- UNESCO Chair for Health Education and Sustainable Development Federico II University of Naples Corso Umberto I, 40 - 80138, Napoli, Centralino, Italy
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Obesity-associated asthma in childhood. Allergol Select 2020; 4:76-85. [PMID: 33134805 PMCID: PMC7592418 DOI: 10.5414/alx02178e] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 08/05/2020] [Indexed: 02/07/2023] Open
Abstract
Obesity and bronchial asthma are very common diseases in children and adolescents, associated with a considerable burden of disease, reduced quality of life and comorbidities. Obesity is a significant risk factor for bronchial asthma. On the one hand, obesity leads to changes in the mechanics and function of the lungs and chest. On the other hand, obesity-associated inflammatory processes with increased production of leptin and cytokines may trigger bronchial inflammation with the appearance of asthmatic symptoms. The diseases are also linked by genetic factors. Physical activity and weight reduction have a significant benefit. Pharmacotherapy must be based on the pattern of inflammation. This article summarizes the current state of the literature on the association of asthma and obesity and presents current and possible future treatment options.
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Liu S, Cao D, Ren Z, Li J, Peng L, Zhang Q, Cheng B, Cheng Z, Ai J, Zheng X, Liu L, Wei Q. The relationships between bariatric surgery and sexual function: current evidence based medicine. BMC Urol 2020; 20:150. [PMID: 33008406 PMCID: PMC7532646 DOI: 10.1186/s12894-020-00707-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Accepted: 08/26/2020] [Indexed: 02/08/2023] Open
Abstract
Background Controversy remains despite several studies have discussed the role of bariatric surgery in improving male’s sexual function. This study aims to evaluate the efficacy of bariatric surgery in promoting male’s erectile function. Methods PubMed, EMbase, The Cochrane Library, CNKI and Clinical Trails.gov were searched from database inception to May 2019. The language of publication was limited in English. The International Index of Erectile Function (IIEF) score and Brief Male Sexual Function Inventory (BSFI) score were set as the primary outcome. Results Eleven studies with a total of 370 patients were enrolled in this meta-analysis. The results showed significant improvement in the IIEF score (erectile function: MD = 5.33, 95% CI 4.12–6.54; intercourse satisfaction: MD = 2.57, 95% CI 1.19–3.94; orgasmic function: MD = 0.50, 95%CI 0.60–0.94; overall satisfaction: MD = 1.67, 95% CI 0.78–2.56; sexual desire: MD = 1.27, 95% CI 0.61–1.93; total erectile function: MD = 7.21, 95% CI 4.33–10.10) and the BSFI score (erection: MD =2.53, 95% CI 2.39–2.67; ejaculation: MD = 1.40, 95% CI 1.28–1.51; desire: MD =1.40, 95% CI 1.32–1.49; problem assessment: MD = 2.20, 95% CI 2.06–2.34; sexual satisfaction: MD = 0.70, 95% CI 0.60–0.76) in obese individuals after bariatric surgery. Conclusions This systematic review and meta-analysis indicated that bariatric surgery could be effective in promoting males’s sexual function for obese individuals.
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Affiliation(s)
- Shengzhuo Liu
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Dehong Cao
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Zhengju Ren
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jinze Li
- DepartmentofUrology, Nanchong CentralHospital, The Second ClinicalMedical College, NorthSichuanMedicalCollege (University), Nanchong, Sichuan, China
| | - Lei Peng
- DepartmentofUrology, Nanchong CentralHospital, The Second ClinicalMedical College, NorthSichuanMedicalCollege (University), Nanchong, Sichuan, China
| | - Qin Zhang
- Department of Radiology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, China
| | - Bo Cheng
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Zheyu Cheng
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jianzhong Ai
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xiaonan Zheng
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Liangren Liu
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
| | - Qiang Wei
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
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Pereira JN, Chactoura J, Nohra F, Diogenes MEL, Bezerra FF. Free and Bioavailable Fractions of Vitamin D: Association with Maternal Characteristics in Brazilian Pregnant Women. J Nutr Metab 2020; 2020:1408659. [PMID: 33014456 PMCID: PMC7519195 DOI: 10.1155/2020/1408659] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 09/01/2020] [Accepted: 09/08/2020] [Indexed: 12/13/2022] Open
Abstract
Normal pregnancy is characterized by many changes in vitamin D metabolism, challenging the assessment of vitamin D status based exclusively on serum total 25-hydroxyvitamin D (25(OH)D). We hypothesized that measuring free and bioavailable fractions contributes to a better vitamin D status assessment in late pregnancy. Our aim was to evaluate a broad set of biomarkers of vitamin D status in Brazilian women in the third trimester of pregnancy. This cross-sectional study was conducted in women (n = 123, 18-44 y, 27-41 wk gestation) attended in a public maternity in Rio de Janeiro (2016-2018). Biomarkers included serum concentrations of total 25(OH)D3, parathyroid hormone (PTH), vitamin D-binding protein (DBP), and free and bioavailable fractions of 25(OH)D3. Vitamin D insufficiency (<50 nmol/L) was prevalent in 47.9% of the pregnant women. Serum 25(OH)D3 was inversely associated with the gestational week (β = -0.71, 95% confidence interval (CI): -1.31 to -0.16) and season, being lower in autumn (β = -9.90, 95% CI: -16.14 to -3.64) and winter (β = -16.74, 95%CI: -23.13 to -10.34). Concentrations of DBP, and free and bioavailable 25(OH)D3 were also inversely associated with winter months (P < 0.05). DBP was directly associated with prepregnancy BMI (β = 5.84, 95% CI: 0.62 to 11.06). The recognized season-effect on total 25(OH)D3 appeared to also occur on free and bioavailable fractions. Although advanced gestational age was associated with lower total 25(OH)D3, our results suggest an adaptive mechanism responsible for maintaining free fraction during the 3rd trimester. We also suggest that starting pregnancy in obese condition may have an impact on vitamin D bioavailability, which deserves further investigation.
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Affiliation(s)
- Joana N. Pereira
- Instituto de Nutrição, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Julia Chactoura
- Instituto de Nutrição, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Fernanda Nohra
- Instituto de Nutrição, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Maria Eduarda L. Diogenes
- Instituto de Nutrição, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
- Instituto Nacional de Câncer José Alencar Gomes da Silva, Rio de Janeiro, Brazil
| | - Flávia F. Bezerra
- Instituto de Nutrição, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
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Siersbæk R, Scabia V, Nagarajan S, Chernukhin I, Papachristou EK, Broome R, Johnston SJ, Joosten SEP, Green AR, Kumar S, Jones J, Omarjee S, Alvarez-Fernandez R, Glont S, Aitken SJ, Kishore K, Cheeseman D, Rakha EA, D'Santos C, Zwart W, Russell A, Brisken C, Carroll JS. IL6/STAT3 Signaling Hijacks Estrogen Receptor α Enhancers to Drive Breast Cancer Metastasis. Cancer Cell 2020; 38:412-423.e9. [PMID: 32679107 PMCID: PMC7116707 DOI: 10.1016/j.ccell.2020.06.007] [Citation(s) in RCA: 166] [Impact Index Per Article: 33.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Revised: 03/20/2020] [Accepted: 06/12/2020] [Indexed: 02/06/2023]
Abstract
The cytokine interleukin-6 (IL6) and its downstream effector STAT3 constitute a key oncogenic pathway, which has been thought to be functionally connected to estrogen receptor α (ER) in breast cancer. We demonstrate that IL6/STAT3 signaling drives metastasis in ER+ breast cancer independent of ER. STAT3 hijacks a subset of ER enhancers to drive a distinct transcriptional program. Although these enhancers are shared by both STAT3 and ER, IL6/STAT3 activity is refractory to standard ER-targeted therapies. Instead, inhibition of STAT3 activity using the JAK inhibitor ruxolitinib decreases breast cancer invasion in vivo. Therefore, IL6/STAT3 and ER oncogenic pathways are functionally decoupled, highlighting the potential of IL6/STAT3-targeted therapies in ER+ breast cancer.
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Affiliation(s)
- Rasmus Siersbæk
- Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
| | - Valentina Scabia
- ISREC - Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
| | - Sankari Nagarajan
- Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK
| | - Igor Chernukhin
- Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK
| | | | - Rebecca Broome
- Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK
| | - Simon J Johnston
- Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK
| | - Stacey E P Joosten
- Division of Oncogenomics, Oncode Institute, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Andrew R Green
- Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK
| | - Sanjeev Kumar
- Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK; Addenbrookes Hospital, Cambridge CB2 0QQ, UK
| | - Julia Jones
- Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK
| | - Soleilmane Omarjee
- Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK
| | | | - Silvia Glont
- Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK
| | - Sarah J Aitken
- Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK; Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK; Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK
| | - Kamal Kishore
- Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK
| | - Danya Cheeseman
- Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK
| | - Emad A Rakha
- Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK
| | - Clive D'Santos
- Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK
| | - Wilbert Zwart
- Division of Oncogenomics, Oncode Institute, Netherlands Cancer Institute, Amsterdam, the Netherlands; Laboratory of Chemical Biology and Institute for Complex Molecular Systems, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands
| | - Alasdair Russell
- Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK
| | - Cathrin Brisken
- ISREC - Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
| | - Jason S Carroll
- Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
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Pillai SS, Lakhani HV, Zehra M, Wang J, Dilip A, Puri N, O’Hanlon K, Sodhi K. Predicting Nonalcoholic Fatty Liver Disease through a Panel of Plasma Biomarkers and MicroRNAs in Female West Virginia Population. Int J Mol Sci 2020; 21:ijms21186698. [PMID: 32933141 PMCID: PMC7554851 DOI: 10.3390/ijms21186698] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Revised: 09/04/2020] [Accepted: 09/11/2020] [Indexed: 02/07/2023] Open
Abstract
(1) Background: Nonalcoholic fatty liver disease (NAFLD) is primarily characterized by the presence of fatty liver, hepatic inflammation and fibrogenesis eventually leading to nonalcoholic steatohepatitis (NASH) or cirrhosis. Obesity and diabetes are common risk factors associated with the development and progression of NAFLD, with one of the highest prevalence of these diseased conditions in the West Virginia population. Currently, the diagnosis of NAFLD is limited to radiologic studies and biopsies, which are not cost-effective and highly invasive. Hence, this study aimed to develop a panel and assess the progressive levels of circulatory biomarkers and miRNA expression in patients at risk for progression to NASH to allow early intervention strategies. (2) Methods: In total, 62 female patients were enrolled and blood samples were collected after 8–10 h of fasting. Computed tomography was performed on abdomen/pelvis following IV contrast administration. The patients were divided into the following groups: Healthy subjects with normal BMI and normal fasting blood glucose (Control, n = 20), Obese with high BMI and normal fasting blood glucose (Obese, n = 20) and Obese with high fasting blood glucose (Obese + DM, n = 22). Based on findings from CT, another subset was created from Obese + DM group with patients who showed signs of fatty liver infiltration (Obese + DM(FI), n = 10). ELISA was performed for measurement of plasma biomarkers and RT-PCR was performed for circulating miRNA expression. (3) Results: Our results show significantly increased levels of plasma IL-6, Leptin and FABP-1, while significantly decreased level of adiponectin in Obese, Obese + DM and Obese + DM(FI) group, as compared to healthy controls. The level of CK-18 was significantly increased in Obese + DM(FI) group as compared to control. Subsequently, the expression of miR-122, miR-34a, miR-375, miR-16 and miR-21 was significantly increased in Obese + DM and Obese + DM(FI) group as compared to healthy control. Our results also show distinct correlation of IL-6, FABP-1 and adiponectin levels with the expression of miRNAs in relation to the extent of NAFLD progression. (4) Conclusion: Our results support the clinical application of these biomarkers and miRNAs in monitoring the progression of NAFLD, suggesting a more advanced diagnostic potential of this panel than conventional methods. This panel may provide an appropriate method for early prognosis and management of NAFLD and subsequent adverse hepatic pathophysiology, potentially reducing the disease burden on the West Virginia population.
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Affiliation(s)
- Sneha S. Pillai
- Departments of Surgery and Biomedical Sciences, Marshall University Joan C. Edwards School of Medicine, Huntington, WV 25701, USA; (S.S.P.); (H.V.L.); (M.Z.); (J.W.); (A.D.)
| | - Hari Vishal Lakhani
- Departments of Surgery and Biomedical Sciences, Marshall University Joan C. Edwards School of Medicine, Huntington, WV 25701, USA; (S.S.P.); (H.V.L.); (M.Z.); (J.W.); (A.D.)
| | - Mishghan Zehra
- Departments of Surgery and Biomedical Sciences, Marshall University Joan C. Edwards School of Medicine, Huntington, WV 25701, USA; (S.S.P.); (H.V.L.); (M.Z.); (J.W.); (A.D.)
| | - Jiayan Wang
- Departments of Surgery and Biomedical Sciences, Marshall University Joan C. Edwards School of Medicine, Huntington, WV 25701, USA; (S.S.P.); (H.V.L.); (M.Z.); (J.W.); (A.D.)
| | - Anum Dilip
- Departments of Surgery and Biomedical Sciences, Marshall University Joan C. Edwards School of Medicine, Huntington, WV 25701, USA; (S.S.P.); (H.V.L.); (M.Z.); (J.W.); (A.D.)
| | - Nitin Puri
- Departments of Biomedical Sciences and Medical Education, Marshall University Joan C. Edwards School of Medicine, Huntington, WV 25701, USA;
| | - Kathleen O’Hanlon
- Departments of Family Medicine, Marshall University Joan C. Edwards School of Medicine, Huntington, WV 25701, USA;
| | - Komal Sodhi
- Departments of Surgery and Biomedical Sciences, Marshall University Joan C. Edwards School of Medicine, Huntington, WV 25701, USA; (S.S.P.); (H.V.L.); (M.Z.); (J.W.); (A.D.)
- Correspondence: ; Tel.: +1-(304)-691-1704; Fax: +1-(914)-347-4956
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Wueest S, Konrad D. The controversial role of IL-6 in adipose tissue on obesity-induced dysregulation of glucose metabolism. Am J Physiol Endocrinol Metab 2020; 319:E607-E613. [PMID: 32715746 DOI: 10.1152/ajpendo.00306.2020] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Interleukin (IL)-6 is a pleotropic cytokine with various physiological and pathophysiological functions in different cells and tissues. In cells residing within white adipose tissue, several, and sometimes conflicting, IL-6 actions have been described in the development of obesity-associated derangements of glucose metabolism. Herein, we aim to summarize opposing findings and discuss recent evidence that IL-6 signaling in adipose tissue is regulated in a depot and cell-specific manner.
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Affiliation(s)
- Stephan Wueest
- Division of Pediatric Endocrinology and Diabetology, University Children's Hospital, Zurich, Switzerland
- Children's Research Center, University Children's Hospital, Zurich, Switzerland
| | - Daniel Konrad
- Division of Pediatric Endocrinology and Diabetology, University Children's Hospital, Zurich, Switzerland
- Children's Research Center, University Children's Hospital, Zurich, Switzerland
- Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
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46
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Role of Adipose Tissue-Derived Autotaxin, Lysophosphatidate Signaling, and Inflammation in the Progression and Treatment of Breast Cancer. Int J Mol Sci 2020; 21:ijms21165938. [PMID: 32824846 PMCID: PMC7460696 DOI: 10.3390/ijms21165938] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Revised: 08/07/2020] [Accepted: 08/14/2020] [Indexed: 12/15/2022] Open
Abstract
Autotaxin (ATX) is a secreted enzyme that produces lysophosphatidate (LPA), which signals through six G-protein coupled receptors, promoting tumor growth, metastasis, and survival from chemotherapy and radiotherapy. Many cancer cells produce ATX, but breast cancer cells express little ATX. In breast tumors, ATX is produced by tumor-associated stroma. Breast tumors are also surrounded by adipose tissue, which is a major bodily source of ATX. In mice, a high-fat diet increases adipocyte ATX production. ATX production in obesity is also increased because of low-level inflammation in the expanded adipose tissue. This increased ATX secretion and consequent LPA signaling is associated with decreased adiponectin production, which results in adverse metabolic profiles and glucose homeostasis. Increased ATX production by inflamed adipose tissue may explain the obesity-breast cancer association. Breast tumors produce inflammatory mediators that stimulate ATX transcription in tumor-adjacent adipose tissue. This drives a feedforward inflammatory cycle since increased LPA signaling increases production of more inflammatory mediators and cyclooxygenase-2. Inhibiting ATX activity, which has implications in breast cancer adjuvant treatments, attenuates this cycle. Targeting ATX activity and LPA signaling may potentially increase chemotherapy and radiotherapy efficacy, and decrease radiation-induced fibrosis morbidity independently of breast cancer type because most ATX is not derived from breast cancer cells.
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Yong HY, Mohd Shariff Z, Mohd Yusof BN, Rejali Z, Tee YYS, Bindels J, van der Beek EM. Independent and combined effects of age, body mass index and gestational weight gain on the risk of gestational diabetes mellitus. Sci Rep 2020; 10:8486. [PMID: 32444832 PMCID: PMC7244566 DOI: 10.1038/s41598-020-65251-2] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Accepted: 04/15/2020] [Indexed: 11/25/2022] Open
Abstract
This study aimed to identify the independent and combined effects of age, BMI at first prenatal visit and GWG on the risk of GDM. A retrospective cohort study of 1,951 pregnant women in Seremban district, Negeri Sembilan, Malaysia. GDM was defined as fasting plasma glucose (FPG) ≥5.6 mmol/l and/or 2-hour postprandial plasma glucose (2hPPG) ≥7.8 mmol/l. A higher percentage of women with GDM had 2 risk factors (29.0%) or >2 risk factors (8.6%) compared to non-GDM women (2 risk factors: 25.5%; >2 risk factors: 5.0%). In general, women with ≥2 risk factors were respectively 1.36-2.06 times more likely to have GDM compared to those without risk factors. Older maternal age and being overweight/obese were significantly associated with risk of GDM. Overweight/obese women with age ≥35 years had 2.45 times higher risk of GDM and having excessive GWG at second trimester further increased the risk of GDM. Age and BMI are independent risk factors for GDM but not GWG in the first and second trimester. The findings emphasize the need to focus on a healthy BMI before pregnancy and optimal GWG during pregnancy to improve pregnancy outcomes.
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Affiliation(s)
- Heng Yaw Yong
- Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia
| | - Zalilah Mohd Shariff
- Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia.
| | - Barakatun Nisak Mohd Yusof
- Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia
| | - Zulida Rejali
- Department of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia
| | - Yvonne Yee Siang Tee
- Danone Specialized Nutrition (Malaysia) Sdn Bhd, 59200, Mid Valley City, Lingkaran Syed Putra, Kuala Lumpur, Malaysia
| | - Jacques Bindels
- Danone Nutricia Research, Uppsalalaan 12, 3584, CT, Utrecht, The Netherlands
| | - Eline M van der Beek
- Danone Nutricia Research, Uppsalalaan 12, 3584, CT, Utrecht, The Netherlands
- Department of Pediatrics, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
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Effect of Bariatric Surgery on Serum Inflammatory Factors of Obese Patients: a Systematic Review and Meta-Analysis. Obes Surg 2020; 29:2631-2647. [PMID: 31093862 DOI: 10.1007/s11695-019-03926-0] [Citation(s) in RCA: 81] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Obesity is one of the main causes of inflammation. Previous studies have reported inconclusive results regarding the effect of bariatric surgery on inflammatory markers. This systematic review and meta-analysis is aimed at describing the effect of bariatric surgery on C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α). PubMed/Medline and Scopus were systematically searched for all eligible studies from inception to June 2018. Results are expressed as weighted mean difference (MD) with 95% confidence intervals (CI) using a random effects model. Overall, 116 studies which evaluated serum CRP, IL-6, and TNF-α after bariatric surgery were included. Pooled effect size showed significant reduction in serum CRP (- 5.30 mg/l, 95% CI - 5.46, - 5.15, P < 0.001), IL-6 (- 0.58 pg/ml, 95% CI - 0.64, - 0.53, P < 0.001), and TNF-α (- 0.20 pg/ml, 95% CI - 0.39, - 0.02, P = 0.031) with significant heterogeneity across studies (> 95% for all factors). Bariatric surgery significantly lowered inflammatory factors; however, baseline BMI, follow-up duration and type of surgery could impact the extent of observed effects.
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Norden PR, Kume T. The Role of Lymphatic Vascular Function in Metabolic Disorders. Front Physiol 2020; 11:404. [PMID: 32477160 PMCID: PMC7232548 DOI: 10.3389/fphys.2020.00404] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 04/06/2020] [Indexed: 12/13/2022] Open
Abstract
In addition to its roles in the maintenance of interstitial fluid homeostasis and immunosurveillance, the lymphatic system has a critical role in regulating transport of dietary lipids to the blood circulation. Recent work within the past two decades has identified an important relationship between lymphatic dysfunction and patients with metabolic disorders, such as obesity and type 2 diabetes, in part characterized by abnormal lipid metabolism and transport. Utilization of several genetic mouse models, as well as non-genetic models of diet-induced obesity and metabolic syndrome, has demonstrated that abnormal lymphangiogenesis and poor collecting vessel function, characterized by impaired contractile ability and perturbed barrier integrity, underlie lymphatic dysfunction relating to obesity, diabetes, and metabolic syndrome. Despite the progress made by these models, the contribution of the lymphatic system to metabolic disorders remains understudied and new insights into molecular signaling mechanisms involved are continuously developing. Here, we review the current knowledge related to molecular mechanisms resulting in impaired lymphatic function within the context of obesity and diabetes. We discuss the role of inflammation, transcription factor signaling, vascular endothelial growth factor-mediated signaling, and nitric oxide signaling contributing to impaired lymphangiogenesis and perturbed lymphatic endothelial cell barrier integrity, valve function, and contractile ability in collecting vessels as well as their viability as therapeutic targets to correct lymphatic dysfunction and improve metabolic syndromes.
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Affiliation(s)
- Pieter R. Norden
- Feinberg Cardiovascular and Renal Research Institute, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
| | - Tsutomu Kume
- Feinberg Cardiovascular and Renal Research Institute, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
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50
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Obesity, Bioactive Lipids, and Adipose Tissue Inflammation in Insulin Resistance. Nutrients 2020; 12:nu12051305. [PMID: 32375231 PMCID: PMC7284998 DOI: 10.3390/nu12051305] [Citation(s) in RCA: 264] [Impact Index Per Article: 52.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 04/29/2020] [Accepted: 04/30/2020] [Indexed: 12/11/2022] Open
Abstract
Obesity is a major risk factor for the development of insulin resistance and type 2 diabetes. The exact mechanism by which adipose tissue induces insulin resistance is still unclear. It has been demonstrated that obesity is associated with the adipocyte dysfunction, macrophage infiltration, and low-grade inflammation, which probably contributes to the induction of insulin resistance. Adipose tissue synthesizes and secretes numerous bioactive molecules, namely adipokines and cytokines, which affect the metabolism of both lipids and glucose. Disorders in the synthesis of adipokines and cytokines that occur in obesity lead to changes in lipid and carbohydrates metabolism and, as a consequence, may lead to insulin resistance and type 2 diabetes. Obesity is also associated with the accumulation of lipids. A special group of lipids that are able to regulate the activity of intracellular enzymes are biologically active lipids: long-chain acyl-CoAs, ceramides, and diacylglycerols. According to the latest data, the accumulation of these lipids in adipocytes is probably related to the development of insulin resistance. Recent studies indicate that the accumulation of biologically active lipids in adipose tissue may regulate the synthesis/secretion of adipokines and proinflammatory cytokines. Although studies have revealed that inflammation caused by excessive fat accumulation and abnormalities in lipid metabolism can contribute to the development of obesity-related insulin resistance, further research is needed to determine the exact mechanism by which obesity-related insulin resistance is induced.
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