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Antonopoulou S. Platelet-Activating Factor-Induced Inflammation in Obesity: A Two-Sided Coin of Protection and Risk. Cells 2025; 14:471. [PMID: 40214425 PMCID: PMC11987740 DOI: 10.3390/cells14070471] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2025] [Revised: 03/18/2025] [Accepted: 03/20/2025] [Indexed: 04/14/2025] Open
Abstract
Obesity, marked by excessive fat accumulation, especially abdominal, is a global health concern with significant public impact. While obesity-associated chronic unresolved inflammation contributes to metabolic dysfunctions, acute inflammation supports healthy adipose tissue remodeling and expansion. Platelet-activating factor (PAF), a "primitive" signaling molecule, is among the key mediators involved in the acute phase of inflammation and in various pathophysiological processes. This article explores the role of PAF in fat accumulation and obesity by reviewing experimental data from cell cultures, animals, and humans. It proposes an emerging biochemical mechanism in an attempt to explain its dual role in the healthy and obese adipose tissue, including also data on PAF's potential involvement in epigenetic mechanisms that may be linked to the "obesity memory". Finally, it highlights the potential of natural PAF modulators in promoting functional adipose tissue, thermogenesis, and obesity prevention through a healthy lifestyle, including a Mediterranean diet rich in PAF weak agonists/PAF receptor antagonists and regular exercise, which help maintain controlled PAF levels. Conversely, in cases of obesity-related systemic inflammation with excessive PAF levels, potent PAF inhibitors like ginkgolide B and rupatadine may help mitigate metabolic dysfunctions with PAFR antagonists potentially enhancing their effects synergistically.
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Affiliation(s)
- Smaragdi Antonopoulou
- Department of Nutrition and Dietetics, School of Health Sciences and Education, Harokopio University, 17671 Athens, Greece
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Nowicka B, Polkowska I, Zeliszewska-Duk P, Torres A, Duk M. Molecular Assessment of Plasma Concentrations of Selected Adipokines and IL-8 in Horses with Back Pain and Comorbid Asthma-Based on Clinical Cases. Animals (Basel) 2025; 15:310. [PMID: 39943080 PMCID: PMC11815831 DOI: 10.3390/ani15030310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Revised: 01/08/2025] [Accepted: 01/14/2025] [Indexed: 02/16/2025] Open
Abstract
Similarly, in humans and horses, thoracic and lumbosacral back pain cause more disability and work interruptions worldwide than any other disease. Given that there are few effective treatments for back pain in humans and animals, primary prevention strategies and a reduction in pain factors may be crucial. In the analysed data obtained for the horses studied, the pattern of changes in adipocytokine concentrations, including resistin, visfatin and leptin, was noted for those with back pain compared to the control animals. Concentrations of selected adipocytokines in horses from the back pain group were different in animals with a coexisting diagnosis of asthma and back dysfunction. Very few studies are available on adipokine concentrations in horses. No information was found in relation to back pain and asthma in these animals. In humans, correlations of back pain and asthma with concentrations of selected adipokines have been described.
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Affiliation(s)
- Beata Nowicka
- Department and Clinic of Animal Surgery, University of Life Sciences in Lublin, Głęboka 30, 20-612 Lublin, Poland;
| | - Izabela Polkowska
- Department and Clinic of Animal Surgery, University of Life Sciences in Lublin, Głęboka 30, 20-612 Lublin, Poland;
| | - Paulina Zeliszewska-Duk
- Department of Horse Breeding and Use, Faculty of Animal Sciences and Bioeconomy, University of Life Sciences in Lublin, Akademicka 13, 20-950 Lublin, Poland;
| | - Anna Torres
- Department of Pediatrics and Adolescent Gynecology, Medical University of Lublin, Chodzki 4, 20-093 Lublin, Poland;
| | - Mariusz Duk
- Department of Electronics and Information Technology, Faculty of Electrical Engineering and Computer Science, Lublin University of Technology, 20-618 Lublin, Poland;
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Ye J, Yin J. Type 2 diabetes: a sacrifice program handling energy surplus. LIFE METABOLISM 2024; 3:loae033. [PMID: 39873003 PMCID: PMC11748514 DOI: 10.1093/lifemeta/loae033] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Revised: 07/30/2024] [Accepted: 09/12/2024] [Indexed: 01/30/2025]
Abstract
Type 2 diabetes mellitus (T2DM) is closely associated with obesity, while interactions between the two diseases remain to be fully elucidated. To this point, we offer this perspective to introduce a set of new insights into the interpretation of T2DM spanning the etiology, pathogenesis, and treatment approaches. These include a definition of T2DM as an energy surplus-induced diabetes characterized by the gradual decline of β cell insulin secretion function, which ultimately aims to prevent the onset of severe obesity through mechanisms of weight loss. The body employs three adaptive strategies in response to energy surplus: the first one is adipose tissue expansion to store the energy for weight gain under normal weight conditions; the second one is insulin resistance to slow down adipose tissue expansion and weight gain under overweight conditions; and the third one is the onset of T2DM following β cell failure to reverse the weight gain in obese conditions. The primary signaling molecules driving the compensatory responses are adenosine derivatives, such as adenosine triphosphate (ATP), acetyl coenzyme A (acetyl-CoA), and reduced nicotinamide adenine dinucleotide (NADH). These molecules exert their effects through allosteric, post-translational, and transcriptional regulation of metabolic pathways. The insights suggest that insulin resistance and T2DM are protective mechanisms in the defense against excessive adiposity to avert severe obesity. The perspective provides a unified framework explaining the interactions between the two diseases and opens new avenues in the study of T2DM.
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Affiliation(s)
- Jianping Ye
- Metabolic Disease Research Center, Zhengzhou Key Laboratory of Obesity Research, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan 450007, China
- Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450052, China
| | - Jun Yin
- Department of Endocrinology and Metabolism, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai 200233, China
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Purcell SA, Craven SA, Limon-Miro AT, Elliott SA, Melanson EL, Tandon P, Prado CM. Total energy expenditure measured using doubly labeled water in adults with major chronic diseases: a systematic review. Am J Clin Nutr 2024; 120:1071-1084. [PMID: 39209153 PMCID: PMC11600028 DOI: 10.1016/j.ajcnut.2024.08.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Revised: 08/19/2024] [Accepted: 08/22/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND Energy requirement assessment is a cornerstone for nutrition practice. The extent to which total energy expenditure (TEE; indicator of energy requirements) has been measured in adults with chronic diseases has not been explored. OBJECTIVES This systematic review aimed to characterize evidence on TEE among individuals with chronic diseases and describe TEE across chronic diseases and in comparison to controls without a chronic disease. METHODS A literature search using terms related to doubly labeled water and TEE was conducted in PubMed, MEDLINE, Web of Science, and Embase. Eligible articles included those that measured TEE using doubly labeled water in adults with a major chronic disease. Methodological quality was determined using the Academy of Nutrition and Dietetics quality criteria checklist. Sample size-weighted TEE was calculated in each chronic disease subgroup. RESULTS Fifty studies were included, of which 15 had a control group. Median sample size was 20 participants, and approximately half of studies were published over 10 y ago. Thirty-five (70%) studies reported resting energy expenditure, and approximately half (k = 26) reported physical activity level. Methodological quality was neutral (k = 25) or positive (k = 23) for most studies. TEE among individual studies ranged from 934 to 3274 kcal/d. Mean weighted TEE was lowest among gastrointestinal (1786 kcal/d) and neurologic (2104 kcal/d) subgroups and highest among cancer (2903 kcal/d), endocrine (2661 kcal/d), and autoimmune (2625 kcal/d) subgroups. Excluding 1 article in cancer survivors resulted in a low TEE in the cancer subgroup (2112 kcal/d). Most studies with a control group reported no differences in TEE between controls and patients; however, only 1 study was powered for between-group comparisons. CONCLUSIONS Energy requirements vary across chronic diseases, although there is insufficient evidence to suggest that TEE in patients with chronic disease is different than that among controls. Further research is needed to inform energy requirement recommendations that consider chronic disease. This review was registered at PROSPERO as CRD42022336500 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=336500).
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Affiliation(s)
- Sarah A Purcell
- Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Centre for Chronic Disease Prevention and Management, Faculty of Medicine, University of British Columbia, Kelowna, British Columbia, Canada; School of Health and Exercise Sciences, University of British Columbia Okanagan, Kelowna, British Columbia, Canada.
| | - Sarah A Craven
- School of Health and Exercise Sciences, University of British Columbia Okanagan, Kelowna, British Columbia, Canada
| | - Ana Teresa Limon-Miro
- Division of Gastroenterology (Liver Unit), Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada; Human Nutrition Research Unit, Department of Agricultural, Food, and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada
| | - Sarah A Elliott
- Alberta Research Centre for Health Evidence, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada; Cochrane Child Health, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
| | - Edward L Melanson
- Division of Endocrinology Metabolism and Diabetes, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States; Division of Geriatric Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
| | - Puneeta Tandon
- Division of Gastroenterology (Liver Unit), Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
| | - Carla M Prado
- Human Nutrition Research Unit, Department of Agricultural, Food, and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada
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Wnorowska K, Młynek K, Puppel K. The Impact of Negative Energy Balance in Holstein-Friesian Cows on the Blood Concentrations of Interleukin-6 and Plasminogen. Metabolites 2024; 14:548. [PMID: 39452929 PMCID: PMC11509748 DOI: 10.3390/metabo14100548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 10/10/2024] [Accepted: 10/11/2024] [Indexed: 10/26/2024] Open
Abstract
Background/Objectives: The negative energy balance activaties of spontaneous lipolysis. This may promotes inflammation within the adipose tissue. The aim of the study was to explain the development of inflammation during increased lactogenesis. It was hypothesized that lipolysis contributes synthesis of interleukin-6 and plasminogen. Methods: The study was in production conditions carried out using Holstein-Friesian cows. The period studied covered time of early lactation. Results: Up to the peak of lactation, milk yield strongly influenced the rate of loss of body condition. This had an impact on with the intensity of the release of the fatty acids. In both cases this relationships strengthened to the peak of production. Oobserved tendencies towards a decrease in the concentration of glucose and an increase in that of leptin. Loss of the body condition and the release of NEFA were were influencing to affect the blood concentrations of interleukin-6 and plasminogen. We have shown that IL-6 has a relatively strong correlation with the NEFA. They correlate with IL-6 independently of EB influence. This may suggest independent associations between these variables, which could potentially be applied in practice. Conclusions: The NEFA release in the long term can increase the inflammatory response within adipose tissue and can intensify the release of interleukin-6 and plasminogen. It is likely that in the initial stage of lactogenesis, the inflammatory process developing within adipose tissue is physiologically justified. Our results can provide background to this little-described area of research.
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Affiliation(s)
- Kalina Wnorowska
- Institute of Zootechnics and Fisheries, University of Siedlce, B. Prusa 14, 08-110 Siedlce, Poland;
| | - Krzysztof Młynek
- Institute of Zootechnics and Fisheries, University of Siedlce, B. Prusa 14, 08-110 Siedlce, Poland;
| | - Kamila Puppel
- Institute of Animal Sciences, Departments of Animal Breeding, Warsaw University of Life Sciences, Ciszewskiego 8, 02-786 Warsaw, Poland;
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Xu S, Lu F, Gao J, Yuan Y. Inflammation-mediated metabolic regulation in adipose tissue. Obes Rev 2024; 25:e13724. [PMID: 38408757 DOI: 10.1111/obr.13724] [Citation(s) in RCA: 17] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 11/04/2023] [Accepted: 01/17/2024] [Indexed: 02/28/2024]
Abstract
Chronic inflammation of adipose tissue is a prominent characteristic of many metabolic diseases. Lipid metabolism in adipose tissue is consistently dysregulated during inflammation, which is characterized by substantial infiltration by proinflammatory cells and high cytokine concentrations. Adipose tissue inflammation is caused by a variety of endogenous factors, such as mitochondrial dysfunction, reactive oxygen species (ROS) production, endoplasmic reticulum (ER) stress, cellular senescence, ceramides biosynthesis and mediators of lipopolysaccharides (LPS) signaling. Additionally, the gut microbiota also plays a crucial role in regulating adipose tissue inflammation. Essentially, adipose tissue inflammation arises from an imbalance in adipocyte metabolism and the regulation of immune cells. Specific inflammatory signals, including nuclear factor-κB (NF-κB) signaling, inflammasome signaling and inflammation-mediated autophagy, have been shown to be involved in the metabolic regulation. The pathogenesis of metabolic diseases characterized by chronic inflammation (obesity, insulin resistance, atherosclerosis and nonalcoholic fatty liver disease [NAFLD]) and recent research regarding potential therapeutic targets for these conditions are also discussed in this review.
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Affiliation(s)
- Shujie Xu
- Department of Plastic and Reconstructive Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Feng Lu
- Department of Plastic and Reconstructive Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jianhua Gao
- Department of Plastic and Reconstructive Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yi Yuan
- Department of Plastic and Reconstructive Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
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Florido Neto AR, Agostini L, Silva LPD, Nunes MT. Therapeutical Potential of T3 as Adjuvant Therapy in Male Alloxan-induced Diabetic Rats. Endocrinology 2024; 165:bqae066. [PMID: 38862394 DOI: 10.1210/endocr/bqae066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 06/03/2024] [Accepted: 06/06/2024] [Indexed: 06/13/2024]
Abstract
Alloxan-induced diabetic rats present with hypothyroidism. When treated with triiodothyronine (T3), glycemia and proinflammatory cytokine expression are downregulated, improving insulin sensitivity. The effectiveness of associating T3 with insulin (replacement dose [6 U] and [3 U]) in controlling glycemia was investigated in this experimental model. Male Wistar rats were made diabetic by alloxan injection and sorted into groups treated or not with insulin (3 or 6 U) associated or not with T3 (1.5 µg 100 g-1 BW) for 28 days. Nondiabetic rats constituted the control group. Fasting glycemia, glucose decay rate, and thyrotropin (TSH) were measured in the blood/serum of all animals. Immunoblotting was used to assess total GLUT4 expression in skeletal muscles and epididymal white adipose tissue. Cytokine and nuclear factor-κB (NF-κB) expression were measured in these tissues and liver. Diabetic rats presented with increased fasting glycemia, inflammatory cytokines, and NF-κB expression, TSH levels, and insulin resistance. In diabetic rats treated with T3 and/or insulin, these parameters were decreased, whereas GLUT4 and anti-inflammatory cytokine expression were increased. T3 combined with 3-U insulin restored the parameters to values of the control group and was more effective at controlling glycemia than 6-U insulin. Thus, a combination of T3 and insulin might represent a promising strategy for diabetes management since it reduces the insulin requirement by half and improves glycemic control of diabetic rats, which could postpone insulin resistance that develops with chronic insulin administration. These findings open a perspective for using thyroid analogues that provide tissue-specific effects, which might result in a potentially more effective treatment of diabetes.
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Affiliation(s)
- Armando Ribeiro Florido Neto
- Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, 05508-000, São Paulo, SP, Brazil
| | - Lucas Agostini
- Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, 05508-000, São Paulo, SP, Brazil
| | - Luciano Pedro da Silva
- Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, 05508-000, São Paulo, SP, Brazil
| | - Maria Tereza Nunes
- Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, 05508-000, São Paulo, SP, Brazil
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Suba Z. DNA Damage Responses in Tumors Are Not Proliferative Stimuli, but Rather They Are DNA Repair Actions Requiring Supportive Medical Care. Cancers (Basel) 2024; 16:1573. [PMID: 38672654 PMCID: PMC11049279 DOI: 10.3390/cancers16081573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 04/05/2024] [Accepted: 04/16/2024] [Indexed: 04/28/2024] Open
Abstract
BACKGROUND In tumors, somatic mutagenesis presumably drives the DNA damage response (DDR) via altered regulatory pathways, increasing genomic instability and proliferative activity. These considerations led to the standard therapeutic strategy against cancer: the disruption of mutation-activated DNA repair pathways of tumors. PURPOSE Justifying that cancer cells are not enemies to be killed, but rather that they are ill human cells which have the remnants of physiologic regulatory pathways. RESULTS 1. Genomic instability and cancer development may be originated from a flaw in estrogen signaling rather than excessive estrogen signaling; 2. Healthy cells with genomic instability exhibit somatic mutations, helping DNA restitution; 3. Somatic mutations in tumor cells aim for the restoration of DNA damage, rather than further genomic derangement; 4. In tumors, estrogen signaling drives the pathways of DNA stabilization, leading to apoptotic death; 5. In peritumoral cellular infiltration, the genomic damage of the tumor induces inflammatory cytokine secretion and increased estrogen synthesis. In the inflammatory cells, an increased growth factor receptor (GFR) signaling confers the unliganded activation of estrogen receptors (ERs); 6. In breast cancer cells responsive to genotoxic therapy, constitutive mutations help the upregulation of estrogen signaling and consequential apoptosis. In breast tumors non-responsive to genotoxic therapy, the possibilities for ER activation via either liganded or unliganded pathways are exhausted, leading to farther genomic instability and unrestrained proliferation. CONCLUSIONS Understanding the real character and behavior of human tumors at the molecular level suggests that we should learn the genome repairing methods of tumors and follow them by supportive therapy, rather than provoking additional genomic damages.
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Affiliation(s)
- Zsuzsanna Suba
- Department of Molecular Pathology, National Institute of Oncology, Ráth György Str. 7-9, H-1122 Budapest, Hungary
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Bertoldo BB, Paulo GO, Furtado TCDS, Pereira TL, Rodrigues V, Rodrigues DBR, de Faria JB, Rosa RC, Pereira SADL. New immunological aspects of peri-implantitis. EINSTEIN-SAO PAULO 2024; 22:eAO0396. [PMID: 38477721 PMCID: PMC10948093 DOI: 10.31744/einstein_journal/2024ao0396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Accepted: 06/07/2023] [Indexed: 03/14/2024] Open
Abstract
BACKGROUND The authors compared the levels of HIF1-α, VEGF, TNF-α, and IL-10 in peri-implant crevicular fluid between patients with or without peri-implantitis. HIF-1α levels were significantly high in the peri-implantitis possibly due to hypoxia triggered by persistent inflammation. OBJECTIVE This study aimed to compare the levels of HIF1-α, VEGF, TNF-α, and IL-10 in the peri-implant crevicular fluid of patients with and without peri-implantitis. METHODS Forty patients, comprising 16 with and 24 without peri-implantitis were selected. RESULTS Patients with peri-implantitis exhibited significantly higher HIF-1α levels than those without peri-implantitis (p=0.0005). TNF-α revealed significant positive correlations with IL-10 (p=0.0008) and VEGF (p=0.0246), whereas HIF-1α and IL-10 levels (p=0.0041) demonstrated a negative and significative correlation in the peri-implantitis group. CONCLUSION This study, for the first time demonstrates the balance of HIF-1α, TNFα, IL-10, and VEGF in peri-implantitis. It shows an elevated HIF-1α levels in patients with peri-implantitis, which could have stemmed from persistent inflammation- triggered hypoxia. Furthermore, the positive correlation between TNF-α and VEGF suggests intensified proinflammatory activity in peri-implantitis. Nevertheless, further studies are essential to understand these immune dynamics in peri-implantitis. BACKGROUND Higher levels of HIF-1α in patients with peri-implantitis occurred possibly due to persistent hypoxia triggered by inflammation. BACKGROUND Tissue hypoxia in peri-implantitis induced increase in HIF-1α consequently increased VEGF and angiogenesis, contributing to the persistence of inflammation.
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Affiliation(s)
- Bárbara Bellocchio Bertoldo
- Universidade Federal do Triângulo MineiroUberabaMGBrazilUniversidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil.
| | | | | | - Thiago Lima Pereira
- Universidade Federal do Triângulo MineiroUberabaMGBrazilUniversidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil.
| | - Virmondes Rodrigues
- Universidade Federal do Triângulo MineiroUberabaMGBrazilUniversidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil.
| | | | - Juliana Barbosa de Faria
- Universidade Federal do Triângulo MineiroUberabaMGBrazilUniversidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil.
| | - Rodrigo César Rosa
- Universidade Federal do Triângulo MineiroUberabaMGBrazilUniversidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil.
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Rezvani R, Shadmand Foumani Moghadam MR, Cianflone K. Acylation stimulating protein/C3adesArg in the metabolic states: role of adipocyte dysfunction in obesity complications. J Physiol 2024; 602:773-790. [PMID: 38305477 DOI: 10.1113/jp285127] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Accepted: 11/27/2023] [Indexed: 02/03/2024] Open
Abstract
Adipose tissue, as an endocrine organ, secretes several adipocyte-derived hormones named 'adipokines' that are implicated in regulating energy haemostasis. Substantial evidence shows that white adipose tissue-derived adipokines mediate the link between obesity-related exogenous factors (like diet and lifestyle) and various biological events (such as pre- and postmenopausal status) that have obesity consequences (cardiometabolic disorders). One of the critical aetiological factors for obesity-related diseases is the dysfunction of adipokine pathways. Acylation-stimulating protein (ASP) is an adipokine that stimulates triglyceride synthesis and storage in adipose tissue by enhancing glucose and fatty acid uptake. ASP acts via its receptor C5L2. The primary objective of this review is to address the existing gap in the literature regarding ASP by investigating its diverse responses and receptor interactions across multiple determinants of obesity. These determinants include diet composition, metabolic disorders, organ involvement, sex and sex hormone levels. Furthermore, this article explores the broader paradigm shift from solely focusing on adipose tissue mass, which contributes to obesity, to considering the broader implications of adipose tissue function. Additionally, we raise a critical question concerning the clinical relevance of the insights gained from this review, both in terms of potential therapeutic interventions targeting ASP and in the context of preventing obesity-related conditions, highlighting the potential of the ASP-C5L2 interaction as a pharmacological target. In conclusion, these findings validate that obesity is a low-grade inflammatory status with multiorgan involvement and sex differences, demonstrating dynamic interactions between immune and metabolic response determinants.
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Affiliation(s)
- Reza Rezvani
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Katherine Cianflone
- Centre de Recherche Institut Universitaire de Cardiologie & Pneumologie de Québec, Université Laval, Québec, Québec, Canada
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Garcia-Carretero R, Vazquez-Gomez O, Gil-Prieto R, Gil-de-Miguel A. Insulin resistance is a cardiovascular risk factor in hypertensive adults without type 2 diabetes mellitus. Wien Klin Wochenschr 2024; 136:101-109. [PMID: 37814058 DOI: 10.1007/s00508-023-02278-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Accepted: 08/27/2023] [Indexed: 10/11/2023]
Abstract
BACKGROUND Metabolic syndrome refers to the association among several cardiovascular risk factors: obesity, dyslipidemia, hyperglycemia, and hypertension. It is associated with increased cardiovascular risk and the development of type 2 diabetes mellitus. Insulin resistance is the underlying mechanism of metabolic syndrome, although its role in increased cardiovascular risk has not been directly identified. OBJECTIVE We investigated the association between insulin resistance and increased cardiovascular risk in hypertensive adults without diabetes mellitus. DESIGN AND PARTICIPANTS We enrolled participants without diabetes from an outpatient setting in a retrospective, longitudinal study. Several demographic, clinical, and laboratory parameters were recorded during the observation period. Plasma insulin and homeostatic model assessment for insulin resistance (HOMA-IR) were used to determine insulin resistance and four cardiovascular events (acute coronary disease, acute cerebrovascular disease, incident heart failure, and cardiovascular mortality) were combined into a single outcome. Logistic regression and Cox proportional hazards models were fitted to evaluate the association between covariates and outcomes. RESULTS We included 1899 hypertensive adults without diabetes with an average age of 53 years (51.3% women, 23% had prediabetes, and 64.2% had metabolic syndrome). In a logistic regression analysis, male sex (odds ratio, OR = 1.66) having high levels of low-density lipoprotein (LDL, OR = 1.01), kidney function (OR = 0.97), and HOMA-IR (OR = 1.06) were associated with the incidence of cardiovascular events; however, in a survival multivariate analysis, only HOMA-IR (hazard ratio, HR 1.4, 95% confidence interval, CI: 1.05-1.87, p = 0.02) and body mass index (HR 1.05, 95% CI: 1.02-1.08, p = 0.002) were considered independent prognostic variables for the development of incident cardiovascular events. CONCLUSION Insulin resistance and obesity are useful for assessing cardiovascular risk in hypertensive people without diabetes but with preserved kidney function. This work demonstrates the predictive value of the measurement of insulin, and therefore of insulin resistance, in an outpatient setting and attending to high-risk patients.
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Affiliation(s)
- Rafael Garcia-Carretero
- Department of Internal Medicine, Mostoles University Hospital, Rey Juan Carlos University (Madrid), Calle Rio Jucar, s/n, 28935, Mostoles (Madrid), Spain.
| | - Oscar Vazquez-Gomez
- Department of Internal Medicine, Mostoles University Hospital, Rey Juan Carlos University (Madrid), Calle Rio Jucar, s/n, 28935, Mostoles (Madrid), Spain
| | - Ruth Gil-Prieto
- Department of Preventive Medicine and Public Health, Rey Juan Carlos University (Madrid), Madrid, Spain
| | - Angel Gil-de-Miguel
- Department of Preventive Medicine and Public Health, Rey Juan Carlos University (Madrid), Madrid, Spain
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Tiwari R, Verma S, Verma N, Verma D, Narayan J. Correlation of serum uric acid levels with certain anthropometric parameters in prediabetic and drug-naive diabetic subjects. Ann Afr Med 2024; 23:13-18. [PMID: 38358165 PMCID: PMC10922179 DOI: 10.4103/aam.aam_40_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 05/22/2023] [Accepted: 06/13/2023] [Indexed: 02/16/2024] Open
Abstract
Introduction Uric acid is produced during the metabolism of nucleotide and adenosine triphosphate and contains the final product of human purine metabolism. It acts both as an antioxidant and pro-inflammatory marker and has a positive association with visceral fat in overweight subjects. The aim of the present study is to find an association of uric acid level with certain anthropometric parameters in subjects having type 2 diabetes. Materials and Methods The study included 124 urban drug-naive diabetic Indian subjects above 18 years of age from the general population of the city of North India. Uric acid concentrations were estimated by the uricase method. Fasting plasma glucose (FPG) concentrations were estimated by the glucose oxidase-peroxidase method. Anthropometric measurements and information on lifestyle factors and disease history were collected through in-person meeting. Results All participants of the study subjects had a body mass index (BMI) of more than 23.5. BMI, waist-to-hip ratio (WHR), waist-to-height ratio, waist circumference, neck circumference, weight, age, sagittal abdominal diameter (SAD), skinfold thickness, and body roundness index were positively correlated with the serum uric acid level. The correlation of weight, BMI, SAD, and WHR was statistically significant. Conclusion We found that serum uric acid level increases as body fat content increases. Statistical data show remarkable results for a significant correlation of uric acid level with BMI, WHR, SAD, and FPG. Hypertrophy occurs as a result of inflammatory processes and oxidative stress when the supply of energy starts to exceed the storage capacity of adipocytes, as a result, adipokines such as interleukin (IL)-1, IL-6, and tumor-necrosis factor-alpha are released more frequently which lead to low-grade chronic inflammation. Uric acid levels are much lean toward visceral obesity than overall body fat content.
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Affiliation(s)
- Ritu Tiwari
- Department of Physiology, King George Medical University, Lucknow, Uttar Pradesh, India
| | - Shivam Verma
- Department of Physiology, King George Medical University, Lucknow, Uttar Pradesh, India
| | - Narsingh Verma
- Department of Physiology, King George Medical University, Lucknow, Uttar Pradesh, India
| | - Dileep Verma
- Department of Physiology, King George Medical University, Lucknow, Uttar Pradesh, India
| | - Jagdish Narayan
- Department of Physiology, King George Medical University, Lucknow, Uttar Pradesh, India
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13
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Lacerda DR, Nunes-Silva A, Silveira ALM, Costa KA, Rodrigues DF, Moraes MM, Pinho V, Menezes GB, Teixeira MM, Wanner SP, Soares DD, Ferreira AVM. Acute exercise modulates the inflammatory response in adipose tissue in both lean and obese mice. Nutrition 2023; 115:112092. [PMID: 37549454 DOI: 10.1016/j.nut.2023.112092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 03/01/2023] [Accepted: 05/19/2023] [Indexed: 08/09/2023]
Abstract
OBJECTIVES Acute physical exercise acts as a metabolic stressor, promoting activation of the immune system, and this response could be relevant in the adipose tissue remodeling process. In addition, some cytokines have important functions in lipolysis. Because chronic exercise improves obesity-related metabolic and inflammatory dysfunction, herein we investigated the effect of acute exercise on the inflammatory responses in the adipose tissues of lean and obese mice. METHODS Lean mice were fed a standard chow diet, whereas obese mice were fed a high-refined carbohydrate diet for 8 wk. Both groups were subjected to 60 min of moderate-intensity exercise. RESULTS In the epididymal adipose tissue of lean mice, exercise enhanced interleukin (IL)-6 and tumor necrosis factor-α levels, which correlated positively with increased serum free fatty acid concentrations. In vivo confocal imaging of epididymal adipose tissue vessels revealed higher recruitment of neutrophils after exercise. Also, the number of leukocytes expressing CD11b+F480- was elevated 6 h after exercise. Similarly, the chemokine (C-X-C motif) ligand 1 level increased at 6 h and remained high until 24 h after exercise. Myeloperoxidase activity was increased at 6, 12, and 24 h after exercise. Surprisingly, however, no changes were observed in epididymal adipose tissue from obese mice, considering proinflammatory cytokines (IL-6 and tumor necrosis factor-α). On the other hand, IL-13, IL-4, and IL-10 levels were higher in obese mice after exercise. CONCLUSIONS These data suggest that acute exercise promotes an inflammatory response in the adipose tissue of lean mice that is observed as part of its role in adipose tissue remodeling. In contrast, acute exercise promotes an antiinflammatory response in adipose tissue from obese mice, likely as an important tool for restoring homeostasis.
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Affiliation(s)
- Débora Romualdo Lacerda
- Department of Nutrition, Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Albená Nunes-Silva
- Department of Physical Education, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil.
| | | | - Kátia Anunciação Costa
- Department of Nutrition, Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Débora Fernandes Rodrigues
- Department of Nutrition, Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Michele Macedo Moraes
- Department of Physical Education, School of Physical Education, Physiotherapy and Occupational Therapy, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Vanessa Pinho
- Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Gustavo Batista Menezes
- Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Mauro Martins Teixeira
- Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Samuel Penna Wanner
- Department of Physical Education, School of Physical Education, Physiotherapy and Occupational Therapy, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Danusa Dias Soares
- Department of Physical Education, School of Physical Education, Physiotherapy and Occupational Therapy, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
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14
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Abstract
Obesity, which has currently reached pandemic dimensions, is usually accompanied by diabetes mellitus type 2 (T2DM). These two conditions share common pathophysiological mechanisms. Adipose tissue secretes cytokines which are involved in inflammation and various endocrine functions. As for T2DM, it is characterized also by inflammation, mitochondrial dysfunction, and hyperinsulinemia. These conditions occur also in other diseases related to obesity and T2DM, like cardiovascular disease (CVD) and nonalcoholic fatty liver disease (NAFLD). Thus, management of obesity-related complications with lifestyle modification, anti-obesity drugs, and bariatric surgery, all contribute to improvement in any of these conditions. This review provides an overview of the literature addressing the association between obesity and T2DM, briefly discussing the pathophysiological mechanisms linking these conditions and outlining the management approach at the overlap of obesity and T2DM.
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Affiliation(s)
- Chrysoula Boutari
- Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration General Hospital, Thessaloniki, Greece; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Antea DeMarsilis
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Christos S Mantzoros
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Medicine, Boston VA Healthcare System, Boston, MA, USA.
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15
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Carica Papaya Reduces High Fat Diet and Streptozotocin-Induced Development of Inflammation in Adipocyte via IL-1β/IL-6/TNF-α Mediated Signaling Mechanisms in Type-2 Diabetic Rats. Curr Issues Mol Biol 2023; 45:852-884. [PMID: 36826001 PMCID: PMC9956039 DOI: 10.3390/cimb45020056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 12/28/2022] [Accepted: 12/31/2022] [Indexed: 01/20/2023] Open
Abstract
The prevalence of obesity in contemporary society has brought attention to how serious it is all around the world. Obesity, a proinflammatory condition defined by hypertrophied adipocytes and immune cells that reside in adipose tissue, is characterized by elevated circulating levels of proinflammatory cytokines. The pro-inflammatory mediators trigger a number of inflammatory pathways and affect the phosphorylation of a number of insulin-signaling pathways in peripheral tissues. In this work, we pointed the outcome of the leaves of Carica papaya (C. papaya) on the inflammatory molecules by in vivo and in silico analysis in order to prove its mechanisms of action. Adipocytokines, antioxidant enzymes, gene and protein expression of pro-inflammatory signaling molecules (mTOR, TNF-α, IL-1β, IL-6 and IKKβ) by q-RT-PCR and immunohistochemistry, as well as histopathological analysis, in adipose tissues were carried out. C. papaya reinstated the levels of adipocytokines, antioxidant enzymes and mRNA levels of mTOR, TNF-α, IL-1β, IL-6 and IKKβ in the adipose tissues of type 2 diabetic rats. Molecular docking and dynamics simulation studies revealed that caffeic acid, transferulic acid and quercetin had the top hit rates against IKKβ, TNF-α, IL-6, IL-1β, and mTOR. This study concludes that C. papaya put back the altered effects in fatty tissue of type 2 diabetic rats by restoring the adipocytokines and the gene expression.
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16
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Bodur C, Kazyken D, Huang K, Tooley AS, Cho KW, Barnes TM, Lumeng CN, Myers MG, Fingar DC. TBK1-mTOR Signaling Attenuates Obesity-Linked Hyperglycemia and Insulin Resistance. Diabetes 2022; 71:2297-2312. [PMID: 35983955 PMCID: PMC9630091 DOI: 10.2337/db22-0256] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Accepted: 08/15/2022] [Indexed: 11/13/2022]
Abstract
The innate immune kinase TBK1 (TANK-binding kinase 1) responds to microbial-derived signals to initiate responses against viral and bacterial pathogens. More recent work implicates TBK1 in metabolism and tumorigenesis. The kinase mTOR (mechanistic target of rapamycin) integrates diverse environmental cues to control fundamental cellular processes. Our prior work demonstrated in cells that TBK1 phosphorylates mTOR (on S2159) to increase mTORC1 and mTORC2 catalytic activity and signaling. Here we investigate a role for TBK1-mTOR signaling in control of glucose metabolism in vivo. We find that mice with diet-induced obesity (DIO) but not lean mice bearing a whole-body "TBK1-resistant" Mtor S2159A knock-in allele (MtorA/A) display exacerbated hyperglycemia and systemic insulin resistance with no change in energy balance. Mechanistically, Mtor S2159A knock-in in DIO mice reduces mTORC1 and mTORC2 signaling in response to insulin and innate immune agonists, reduces anti-inflammatory gene expression in adipose tissue, and blunts anti-inflammatory macrophage M2 polarization, phenotypes shared by mice with tissue-specific inactivation of TBK1 or mTOR complexes. Tissues from DIO mice display elevated TBK1 activity and mTOR S2159 phosphorylation relative to lean mice. We propose a model whereby obesity-associated signals increase TBK1 activity and mTOR phosphorylation, which boost mTORC1 and mTORC2 signaling in parallel to the insulin pathway, thereby attenuating insulin resistance to improve glycemic control during diet-induced obesity.
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Affiliation(s)
- Cagri Bodur
- Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI
| | - Dubek Kazyken
- Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI
| | - Kezhen Huang
- Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI
| | - Aaron Seth Tooley
- Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI
| | - Kae Won Cho
- Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI
| | - Tammy M. Barnes
- Department of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan Medical School, Ann Arbor, MI
| | - Carey N. Lumeng
- Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI
| | - Martin G. Myers
- Department of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan Medical School, Ann Arbor, MI
| | - Diane C. Fingar
- Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI
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17
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Luo H, Wu P, Chen X, Wang B, Chen G, Su X. Novel insights into the relationship between α-1 anti-trypsin with the pathological development of cardio-metabolic disorders. Int Immunopharmacol 2022; 111:109077. [PMID: 35907338 DOI: 10.1016/j.intimp.2022.109077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Revised: 07/09/2022] [Accepted: 07/18/2022] [Indexed: 11/05/2022]
Abstract
According to the previous studies, chronic low-grade systemic inflammatory response has been shown to be significantly associated with the pathological development of cardio-metabolic disorder diseases, including atherosclerosis, type 2 diabetes mellitus, and non-alcoholic fatty liver disease (NAFLD). On the other hand, auto-immunity process could also facilitate the pathogenesis of type 1 diabetes mellitus importantly. Concerning on this notion, the anti-inflammatory therapeutic strategy is demonstrated to embrace an essential function in those cardio-metabolic disorders in clinical practice. The α-1 anti-trypsin, also named Serpin-A1 and as an acute phase endogenous protein, has been verified to have several modulatory effects such as anti-inflammatory response, anti-apoptosis, and immunomodulatory functions. In addition, it is also used for therapeutic strategy of a rare genetic disease caused by the deficiency of α-1 anti-trypsin. Recent emerging evidence has indicated that the serum concentrations of α-1 anti-trypsin levels and its biological activity are significantly changed in those inflammatory and immune related cardio-metabolic disorder diseases. Nevertheless, the underlying mechanism is still not elucidated. In the current review, the basic experiments and clinical trials which provided the evidence revealing the potential therapeutic function of the α-1 anti-trypsin in cardio-metabolic disorder diseases were well-summarized. Furthermore, the results which indicated that the α-1 anti-trypsin presented the possibility as a novel serum biomarker in humans to predict those cardio-metabolic disorder diseases were also elucidated.
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Affiliation(s)
- Haizhen Luo
- Department of Cardiology, the Fuding Hospital of Fujian University of Traditional Chinese Medicine, Fuding, Fujian, China
| | - Penglong Wu
- Department of Cardiology, the Xiamen Cardiovascular Hospital of Xiamen University, Xiamen, Fujian, China
| | - Xiang Chen
- Department of Cardiology, the Xiamen Cardiovascular Hospital of Xiamen University, Xiamen, Fujian, China
| | - Bin Wang
- Department of Cardiology, the Xiamen Cardiovascular Hospital of Xiamen University, Xiamen, Fujian, China
| | - Geng Chen
- Department of Cardiology, the Fuding Hospital of Fujian University of Traditional Chinese Medicine, Fuding, Fujian, China.
| | - Xin Su
- Department of Cardiology, the Xiamen Cardiovascular Hospital of Xiamen University, Xiamen, Fujian, China.
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18
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Zhang X, Ostrov DA, Tian H. Alpha-1 antitrypsin: A novel biomarker and potential therapeutic approach for metabolic diseases. Clin Chim Acta 2022; 534:71-76. [PMID: 35810800 DOI: 10.1016/j.cca.2022.07.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Revised: 07/02/2022] [Accepted: 07/05/2022] [Indexed: 02/05/2023]
Abstract
It is well recognized that chronic low-grade systemic inflammation and autoimmunity contribute to the pathogenesis of metabolic syndrome, its associated diseases (e.g. type 2 diabetes, non-alcoholic fatty liver disease) and type 1 diabetes, respectively. Consequently, anti-inflammatory agents might play a role in managing these immune associated metabolic diseases. Alpha-1 antitrypsin (AAT), an endogenous acute phase protein being used for treatment of AAT deficiency (a rare genetic disease), has multiple functions including anti-inflammatory, immunomodulatory, anti-apoptosis and cytoprotective effects. In this review, we summarized basic and clinical studies that reported potential therapeutic role of AAT in metabolic syndrome associated diseases and type 1 diabetes. Studies that demonstrated AAT had the possibility to be used as a novel biomarker to predict these immune associated metabolic diseases were also included.
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Affiliation(s)
- Xiaojuan Zhang
- Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, China
| | - David A Ostrov
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32611, USA
| | - Haoming Tian
- Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, China.
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19
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Yu L, Zhang X, Ye S, Lian H, Wang H, Ye J. Obesity and COVID-19: Mechanistic Insights From Adipose Tissue. J Clin Endocrinol Metab 2022; 107:1799-1811. [PMID: 35262698 PMCID: PMC8992328 DOI: 10.1210/clinem/dgac137] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Indexed: 02/08/2023]
Abstract
Obesity is associated with an increase in morbidity and mortality from coronavirus disease 2019 (COVID-19). The risk is related to the cytokine storm, a major contributor to multiorgan failure and a pathological character of COVID-19 patients with obesity. While the exact cause of the cytokine storm remains elusive, disorders in energy metabolism has provided insights into the mechanism. Emerging data suggest that adipose tissue in obesity contributes to the disorders in several ways. First, adipose tissue restricts the pulmonary function by generation of mechanical pressures to promote systemic hypoxia. Second, adipose tissue supplies a base for severe acute respiratory syndrome coronavirus 2 entry by overexpression of viral receptors [angiotensin-converting enzyme 2 and dipeptidyl peptidase 4]. Third, impaired antiviral responses of adipocytes and immune cells result in dysfunction of immunologic surveillance as well as the viral clearance systems. Fourth, chronic inflammation in obesity contributes to the cytokine storm by secreting more proinflammatory cytokines. Fifth, abnormal levels of adipokines increase the risk of a hyperimmune response to the virus in the lungs and other organs to enhance the cytokine storm. Mitochondrial dysfunction in adipocytes, immune cells, and other cell types (endothelial cells and platelets, etc) is a common cellular mechanism for the development of cytokine storm, which leads to the progression of mild COVID-19 to severe cases with multiorgan failure and high mortality. Correction of energy surplus through various approaches is recommended in the prevention and treatment of COVID-19 in the obese patients.
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Affiliation(s)
- Lili Yu
- Department of Immunology, Institute of Precision Medicine, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, China
| | - Xiaoying Zhang
- Metabolic Disease Research Center, Zhengzhou University Affiliated Zhengzhou Central Hospital, Zhengzhou 450007, China
| | - Sarah Ye
- Medical College of Georgia at Augusta University, Augusta, Georgia, USA
| | - Hongkai Lian
- Metabolic Disease Research Center, Zhengzhou University Affiliated Zhengzhou Central Hospital, Zhengzhou 450007, China
| | - Hui Wang
- Henan Key Laboratory of Immunology and Targeted Therapy, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China
| | - Jianping Ye
- Metabolic Disease Research Center, Zhengzhou University Affiliated Zhengzhou Central Hospital, Zhengzhou 450007, China
- Center for Advanced Medicine, College of Medicine, Zhengzhou University, Zhengzhou 450007, China
- Corresponding author:
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20
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Green Coffee Bean Extract Normalize Obesity-Induced Alterations of Metabolic Parameters in Rats by Upregulating Adiponectin and GLUT4 Levels and Reducing RBP-4 and HOMA-IR. Life (Basel) 2022; 12:life12050693. [PMID: 35629362 PMCID: PMC9144088 DOI: 10.3390/life12050693] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 04/28/2022] [Accepted: 05/04/2022] [Indexed: 11/28/2022] Open
Abstract
Obesity is a serious public health issue worldwide. Finding safe and efficacious products to reverse obesity has proven to be a difficult challenge. This study showed the effects of Coffea arabica or green coffee bean extract (GCBE) on obesity disorders and the improvement of obesity-induced insulin resistance, dyslipidemia, and inflammation. The active constituents of GCBE were identified via high-performance liquid chromatography. Twenty-four male albino Wistar rats were divided into two groups. The first group (Group I) was fed a control diet, whereas the second group was fed a high-fat diet (HFD) for eight weeks till obesity induction. The second group was equally subdivided into Group II, which received HFD, and Group III, which received HFD + GCBE for another eight weeks. The body and organ weights of the animals were measured, and blood and adipose tissue samples were collected for analysis. The results indicated that the administration of GCBE significantly decreased the body and organ weights. Furthermore, it had an ameliorative effect on serum biochemical parameters. It dramatically reduced total cholesterol, triacylglycerol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, glucose, and insulin levels. In addition, an improvement in homeostasis model assessment-insulin resistance and an enhancement of high-density lipoprotein cholesterol levels were observed compared with the HFD group. In addition, the group treated with GCBE exhibited a marked increase in serum levels of adiponectin (an anti-inflammatory adipokine). In addition, a considerable reduction in adipocyte hypertrophy was found following GCBE treatment. Remarkably, the administration of GCBE resulted in a remarkable decrease in the expression of RBP4 (a pro-inflammatory cytokine), whereas an increase in GLLUT4 expression was observed in the adipose tissue. This improved insulin resistance in GCBE-administered HFD rats compared with other HFD rats. Our study showed that GCBE exhibits anti-obesity activity and may be used as a natural supplement to prevent and treat obesity and its associated disorders.
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21
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Parafiniuk K, Skiba W, Pawłowska A, Suszczyk D, Maciejczyk A, Wertel I. The Role of the Adipokine Resistin in the Pathogenesis and Progression of Epithelial Ovarian Cancer. Biomedicines 2022; 10:920. [PMID: 35453670 PMCID: PMC9028191 DOI: 10.3390/biomedicines10040920] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 04/14/2022] [Accepted: 04/15/2022] [Indexed: 02/07/2023] Open
Abstract
Obesity is a civilization disease associated with an increased risk of developing cardiovascular diseases, diabetes, and some malignancies. The results concerning the relationship between obesity and epithelial ovarian cancer (EOC) are inconclusive. The higher incidence of neoplasms in obese subjects has led to the development of the adipokine hypothesis. Omental adipocyte cells interact with cancer cells, promoting their migration and metastasis via the secretion of adipokines, growth factors, and hormones. One of the adipokines is resistin. It was shown in vitro that resistin stimulates the growth and differentiation of ovarian cancer cells. Moreover, it increases the level of angiogenesis factors, e.g., matrix metalloproteinase 2 (MMP-2) and vascular epithelial growth factor (VEGF). Additionally, resistin induces epithelial-mesenchymal transition (EMT) and stemness in EOC cell lines. A positive correlation has been shown between a higher level of resistin expression and the stage of histological differentiation of EOC or the occurrence of lymph node metastases. In addition, the overexpression of resistin has been found to act as an independent factor determining disease-free survival as well as overall survival in EOC patients. Growing evidence supports the finding that resistin plays an important role in some mechanisms leading to the progression of EOC, though this issue still requires further research.
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Affiliation(s)
- Klaudia Parafiniuk
- Independent Laboratory of Cancer Diagnostics and Immunology, Department of Oncological Gynaecology and Gynaecology, Faculty of Medicine, Medical University of Lublin, Chodźki 4a, 20-093 Lublin, Poland; (K.P.); (A.P.); (D.S.); (A.M.); (I.W.)
| | - Wiktoria Skiba
- Independent Laboratory of Cancer Diagnostics and Immunology, Department of Oncological Gynaecology and Gynaecology, Faculty of Medicine, Medical University of Lublin, Chodźki 4a, 20-093 Lublin, Poland; (K.P.); (A.P.); (D.S.); (A.M.); (I.W.)
| | - Anna Pawłowska
- Independent Laboratory of Cancer Diagnostics and Immunology, Department of Oncological Gynaecology and Gynaecology, Faculty of Medicine, Medical University of Lublin, Chodźki 4a, 20-093 Lublin, Poland; (K.P.); (A.P.); (D.S.); (A.M.); (I.W.)
| | - Dorota Suszczyk
- Independent Laboratory of Cancer Diagnostics and Immunology, Department of Oncological Gynaecology and Gynaecology, Faculty of Medicine, Medical University of Lublin, Chodźki 4a, 20-093 Lublin, Poland; (K.P.); (A.P.); (D.S.); (A.M.); (I.W.)
| | - Aleksandra Maciejczyk
- Independent Laboratory of Cancer Diagnostics and Immunology, Department of Oncological Gynaecology and Gynaecology, Faculty of Medicine, Medical University of Lublin, Chodźki 4a, 20-093 Lublin, Poland; (K.P.); (A.P.); (D.S.); (A.M.); (I.W.)
- Department of Functional Anatomy and Cytobiology, Institute of Biological Sciences, Maria Curie-Sklodowska University, Akademicka 19, 20-033 Lublin, Poland
| | - Iwona Wertel
- Independent Laboratory of Cancer Diagnostics and Immunology, Department of Oncological Gynaecology and Gynaecology, Faculty of Medicine, Medical University of Lublin, Chodźki 4a, 20-093 Lublin, Poland; (K.P.); (A.P.); (D.S.); (A.M.); (I.W.)
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22
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Basolo A, Poma AM, Giannini R, Ceccarini G, Pelosini C, Fierabracci P, Castany MU, Bechi Genzano S, Ambrosini CE, Materazzi G, Chiovato L, Basolo F, Santini F, Torregrossa L. Histological pattern and gene expression profiling of thyroid tissue in subjects with obesity. J Endocrinol Invest 2022; 45:413-423. [PMID: 34392500 DOI: 10.1007/s40618-021-01662-w] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Accepted: 08/10/2021] [Indexed: 01/19/2023]
Abstract
PURPOSE Subjects with obesity may exhibit an increase in serum TSH concentrations. Several mechanisms have been proposed to explain this association, including the presence of a compensatory mechanism to counterbalance an accelerated turnover of thyroid hormones in subjects with obesity. This study aimed at evaluating whether the thyroids of subjects with obesity differs from those of normal-weight individuals regarding histology and gene expression profiling. METHODS Ninety-eight patients were selected among those scheduled for thyroidectomy. At histology, thyroid tissue samples were investigated for the presence of adipocytes and/or lymphocyte infiltration. In a subset of patients, the expression at mRNA level of several genes involved in metabolic pathways and immune cell-related mechanisms was quantified by NanoString Technology. RESULTS The presence of adipose cells was documented in thyroid specimens from 40% normal weight, 52.9% overweight and 73.5% patients with obesity. The number of infiltrating adipocytes was greater in specimens of patients with overweight or obesity compared to normal weight. The lymphocytes common antigen (CD45) and mast cell (MC) scores, and the number of CD3+ and CD8+ lymphocytes were higher in patients with overweight and obesity than in normal-weight subjects. Several genes involved in metabolic pathways were differently expressed in patients with overweight or obesity compared to normal weight, with upregulation of Leptin receptor and downregulation of Fatty Acid-Binding Protein 5. CONCLUSIONS Increased BMI is associated with adipocyte and lymphocyte infiltration of the thyroid, not related to an autoimmune process, which might affect thyroid function in subjects with obesity. A differential gene expression profiling of metabolic and immune pathways in thyroid tissues of patients with obesity was also observed.
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Affiliation(s)
- A Basolo
- Obesity and Lipodystrophy Center, Endocrinology Unit, University Hospital of Pisa, Pisa, Italy.
- Department of Clinical and Experimental Medicine, University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
| | - A M Poma
- Department of Surgical, Medical, Molecular Pathology and Critical Area, University Hospital of Pisa, Pisa, Italy
| | - R Giannini
- Department of Surgical, Medical, Molecular Pathology and Critical Area, University Hospital of Pisa, Pisa, Italy
| | - G Ceccarini
- Obesity and Lipodystrophy Center, Endocrinology Unit, University Hospital of Pisa, Pisa, Italy
| | - C Pelosini
- Obesity and Lipodystrophy Center, Endocrinology Unit, University Hospital of Pisa, Pisa, Italy
- Chemistry and Endocrinology Laboratory, University Hospital of Pisa, Pisa, Italy
| | - P Fierabracci
- Obesity and Lipodystrophy Center, Endocrinology Unit, University Hospital of Pisa, Pisa, Italy
| | - M U Castany
- Department of Surgical, Medical, Molecular Pathology and Critical Area, University Hospital of Pisa, Pisa, Italy
| | - S Bechi Genzano
- Obesity and Lipodystrophy Center, Endocrinology Unit, University Hospital of Pisa, Pisa, Italy
| | - C E Ambrosini
- Department of Surgical, Medical, Molecular Pathology and Critical Area, University Hospital of Pisa, Pisa, Italy
| | - G Materazzi
- Department of Surgical, Medical, Molecular Pathology and Critical Area, University Hospital of Pisa, Pisa, Italy
| | - L Chiovato
- Laboratory for Endocrine Disruptors, Unit of Internal Medicine and Endocrinology, Istituti Clinici Scientifici Maugeri IRCCS, University of Pavia, 27100, Pavia, Italy
- Department of Internal Medicine and Therapeutics, University of Pavia, Via S. Maugeri 4, 27100, Pavia, PV, Italy
| | - F Basolo
- Department of Surgical, Medical, Molecular Pathology and Critical Area, University Hospital of Pisa, Pisa, Italy
| | - F Santini
- Obesity and Lipodystrophy Center, Endocrinology Unit, University Hospital of Pisa, Pisa, Italy
| | - L Torregrossa
- Department of Surgical, Medical, Molecular Pathology and Critical Area, University Hospital of Pisa, Pisa, Italy
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23
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Nouri-Majd S, Salari-Moghaddam A, Keshteli AH, Esmaillzadeh A, Adibi P. Dietary Inflammatory Potential in relation to General and Abdominal Obesity. Int J Clin Pract 2022; 2022:5685249. [PMID: 35685556 PMCID: PMC9159184 DOI: 10.1155/2022/5685249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 01/11/2022] [Accepted: 01/15/2022] [Indexed: 11/20/2022] Open
Abstract
Background/Aims: Limited data are available on the association of Dietary Inflammatory Potential (DIP) with general and abdominal obesity in developing countries. The aim of this study was to examine the association between DIP score with general and abdominal obesity among Iranian adults. Methods. This cross-sectional study was conducted among adults in Isfahan, Iran. Dietary intakes were assessed by using a validated, self-administrated, dish-based, semiquantitative food frequency questionnaire. DIP was calculated based on standard method. Data regarding height, weight, and waist circumference (WC) were collected using a self-reported questionnaire. Overweight or obesity was defined as body mass index (BMI) ≥25 kg/m2, and abdominal obesity was defined as WC ≥ 80 cm for women and ≥94 cm for men. Results. Mean age of study participants was 36.8 ± 8.08 years. The prevalence of general and abdominal obesity was 46.5% and 52.9%, respectively. We observed that higher DIP scores were significantly associated with a lower odds of general obesity (OR: 0.66; 95% CI: 0.58-0.74). Stratified by sex, this significant association was seen only for women (OR: 0.58; 95% CI: 0.46-0.72). In addition, no significant association was found between DIP scores and abdominal obesity. Conclusions. We found a significant inverse association between consumption of a proinflammatory diet and general obesity. In the gender-stratified analysis, this was seen in women, but not in men. There was no significant association between the DIP scores and abdominal obesity.
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Affiliation(s)
- Saeedeh Nouri-Majd
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Asma Salari-Moghaddam
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Ammar Hassanzadeh Keshteli
- Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
- Integrative Functional Gastroenterology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Ahmad Esmaillzadeh
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
- Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
- Obesity and Eating Habits Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Peyman Adibi
- Integrative Functional Gastroenterology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
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24
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Simas AM, Kramer CD, Genco CA. Diet-Induced Non-alcoholic Fatty Liver Disease and Associated Gut Dysbiosis Are Exacerbated by Oral Infection. FRONTIERS IN ORAL HEALTH 2022; 2:784448. [PMID: 35141703 PMCID: PMC8820505 DOI: 10.3389/froh.2021.784448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Accepted: 12/29/2021] [Indexed: 11/13/2022] Open
Abstract
Increasing evidence indicates that chronic inflammation due to periodontal disease is associated with progression of non-alcoholic fatty liver disease (NAFLD) caused by a Western diet. NAFLD has also been associated with oral infection with the etiological agent of periodontal disease, Porphyromonas gingivalis. P. gingivalis oral infection has been shown to induce cardiometabolic disease features including hepatic lipid accumulation while also leading to dysbiosis of the gut microbiome. However, the impact of P. gingivalis infection on the gut microbiota of mice with diet-induced NAFLD and the potential for those changes to mediate NAFLD progression has yet to be determined. In the current study, we have demonstrated that P. gingivalis infection induced sustained alterations of the gut microbiota composition and predicted functions, which was associated with the promotion of NAFLD in steatotic mice. Reduced abundance of short-chain fatty acid-producing microbiota was observed after both acute and chronic P. gingivalis infection. Collectively, our findings demonstrate that P. gingivalis infection produces a persistent change in the gut microbiota composition and predicted functions that promotes steatosis and metabolic disease.
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Affiliation(s)
- Alexandra M. Simas
- Gerald J. and Dorothy R. Friedman School of Nutrition and Science Policy, Graduate Program in Biochemical and Molecular Nutrition, Tufts University, Boston, MA, United States
- Department of Immunology, Tufts University School of Medicine, Boston, MA, United States
| | - Carolyn D. Kramer
- Department of Immunology, Tufts University School of Medicine, Boston, MA, United States
| | - Caroline A. Genco
- Department of Immunology, Tufts University School of Medicine, Boston, MA, United States
- Graduate Program in Immunology, Graduate School of Biomedical Sciences, Tufts University, Boston, MA, United States
- Graduate Program in Molecular Microbiology, Graduate School of Biomedical Sciences, Tufts University, Boston, MA, United States
- *Correspondence: Caroline A. Genco
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25
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Zeytinli Aksit M, Demet Arslan F, Karakoyun I, Aydin C, Turgut E, Parildar H, Gokbalci U, Isbilen Basok B, Duman C, Emiroglu M. Galectin-3 levels and inflammatory response in patients undergoing bariatric surgery. Cytokine 2022; 151:155793. [PMID: 35032862 DOI: 10.1016/j.cyto.2022.155793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 12/03/2021] [Accepted: 12/29/2021] [Indexed: 11/03/2022]
Abstract
PURPOSE Obesity, a low-grade systemic inflammatory disease, causes inflammation in metabolic tissues. Galectin-3(Gal-3) is one of the lectin molecules involved in inflammatory processes. We evaluated the possible relationship between Gal-3 level and the metabolic inflammatory process before and after obesity surgery. METHODS One hundred participants were included in the study and classified as normal weight, overweight, Class I, II, and III obese. Class III obese group underwent bariatric surgery and evaluated in the 3rd and 6th months after surgery. Glucose, insulin, glycated hemoglobin A1c (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR), high sensitivity C-reactive protein (hsCRP), Gal-3, interleukin (IL)-6, IL-10, adiponectin, and leptin levels were determined. RESULTS Gal-3 levels were higher in Class III obese compared to the normal weight group. Postoperative leptin and hsCRP levels were decreased significantly, but the decrease in IL-6 and Gal-3 levels were not significant. Postoperative increased adiponectin and IL-10 levels were significant. Gal-3 was found significantly higher in insulin resistant group. The correlation between Gal-3 with BMI, adiponectin, leptin, hsCRP levels, and HOMA-IR was found weak. CONCLUSION These findings might support the fact that Gal-3 is one of the molecules involved in the linkage between insulin resistance and meta-inflammation in morbid obese.
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Affiliation(s)
- Merve Zeytinli Aksit
- Department of Medical Biochemistry, University of Health Sciences, Tepecik Training and Research Hospital, Izmir, Turkey.
| | - Fatma Demet Arslan
- Department of Medical Biochemistry, University of Health Sciences, Tepecik Training and Research Hospital, Izmir, Turkey
| | - Inanc Karakoyun
- Department of Medical Biochemistry, University of Health Sciences, Tepecik Training and Research Hospital, Izmir, Turkey
| | - Cengiz Aydin
- Department of General Surgery, University of Health Sciences, Tepecik Training and Research Hospital, Izmir, Turkey
| | - Emre Turgut
- Department of General Surgery, University of Health Sciences, Tepecik Training and Research Hospital, Izmir, Turkey
| | - Hulya Parildar
- Department of Family Medicine, University of Health Sciences, Tepecik Training and Research Hospital, Izmir, Turkey
| | - Umut Gokbalci
- Department of Family Medicine, University of Health Sciences, Tepecik Training and Research Hospital, Izmir, Turkey
| | - Banu Isbilen Basok
- Department of Medical Biochemistry, University of Health Sciences, Tepecik Training and Research Hospital, Izmir, Turkey
| | - Can Duman
- Department of Medical Biochemistry, University of Health Sciences, Tepecik Training and Research Hospital, Izmir, Turkey
| | - Mustafa Emiroglu
- Department of General Surgery, University of Health Sciences, Tepecik Training and Research Hospital, Izmir, Turkey
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26
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Costa KA, Lacerda DR, Silveira ALM, Martins LB, Oliveira MC, Rezende BM, Menezes-Garcia Z, Mügge FLB, Silva AM, Teixeira MM, Rouault C, Pinho V, Marcelin G, Clément K, Ferreira AVM. PAF signaling plays a role in obesity-induced adipose tissue remodeling. Int J Obes (Lond) 2022; 46:68-76. [PMID: 34493775 DOI: 10.1038/s41366-021-00961-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Revised: 08/16/2021] [Accepted: 08/26/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND/OBJECTIVES Platelet-activating factor receptor (PAFR) activation controls adipose tissue (AT) expansion in animal models. Our objective was twofold: (i) to check whether PAFR signaling is involved in human obesity and (ii) investigate the PAF pathway role in hematopoietic or non-hematopoietic cells to control adipocyte size. MATERIALS/SUBJECTS AND METHODS Clinical parameters and adipose tissue gene expression were evaluated in subjects with obesity. Bone marrow (BM) transplantation from wild-type (WT) or PAFR-/- mice was performed to obtain chimeric PAFR-deficient mice predominantly in hematopoietic or non-hematopoietic-derived cells. A high carbohydrate diet (HC) was used to induce AT remodeling and evaluate in which cell compartment PAFR signaling modulates it. Also, 3T3-L1 cells were treated with PAF to evaluate fat accumulation and the expression of genes related to it. RESULTS PAFR expression in omental AT from humans with obesity was negatively correlated to different corpulence parameters and more expressed in the stromal vascular fraction than adipocytes. Total PAFR-/- increased adiposity compared with WT independent of diet-induced obesity. Differently, WT mice receiving PAFR-/--BM exhibited similar adiposity gain as WT chimeras. PAFR-/- mice receiving WT-BM showed comparable augmentation in adiposity as total PAFR-/- mice, demonstrating that PAFR signaling modulates adipose tissue expansion through non-hematopoietic cells. Indeed, the PAF treatment in 3T3-L1 adipocytes reduced fat accumulation and expression of adipogenic genes. CONCLUSIONS Therefore, decreased PAFR signaling may favor an AT accumulation in humans and animal models. Importantly, PAFR signaling, mainly in non-hematopoietic cells, especially in adipocytes, appears to play a significant role in regulating diet-induced AT expansion.
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Affiliation(s)
- Kátia A Costa
- Immunometabolism, Department of Nutrition, Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Débora R Lacerda
- Immunometabolism, Department of Nutrition, Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Ana L M Silveira
- Immunometabolism, Department of Nutrition, Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Laís B Martins
- Immunometabolism, Department of Nutrition, Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Marina C Oliveira
- Immunometabolism, Department of Nutrition, Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Barbara M Rezende
- Department of Basic Nursing, Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Zélia Menezes-Garcia
- Department of Microbiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Fernanda L B Mügge
- Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Aristóbolo M Silva
- Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Mauro M Teixeira
- Immunopharmacology, Department of Immunology and Biochemistry, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Christine Rouault
- Sorbonne Université, INSERM, Nutrition and obesities: systemic approaches (Nutriomics), Paris, France.,Assistance Publique Hôpitaux de Paris, Nutrition Departments, CRNH Ile de France, Pitié-Salpêtrière Hospital, Paris, France
| | - Vanessa Pinho
- Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Geneviève Marcelin
- Sorbonne Université, INSERM, Nutrition and obesities: systemic approaches (Nutriomics), Paris, France.,Assistance Publique Hôpitaux de Paris, Nutrition Departments, CRNH Ile de France, Pitié-Salpêtrière Hospital, Paris, France
| | - Karine Clément
- Sorbonne Université, INSERM, Nutrition and obesities: systemic approaches (Nutriomics), Paris, France.,Assistance Publique Hôpitaux de Paris, Nutrition Departments, CRNH Ile de France, Pitié-Salpêtrière Hospital, Paris, France
| | - Adaliene V M Ferreira
- Immunometabolism, Department of Nutrition, Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
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27
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García-Estévez L, Cortés J, Pérez S, Calvo I, Gallegos I, Moreno-Bueno G. Obesity and Breast Cancer: A Paradoxical and Controversial Relationship Influenced by Menopausal Status. Front Oncol 2021; 11:705911. [PMID: 34485137 PMCID: PMC8414651 DOI: 10.3389/fonc.2021.705911] [Citation(s) in RCA: 82] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 07/22/2021] [Indexed: 12/27/2022] Open
Abstract
Breast cancer is the most common tumor in women worldwide, and an increasing public health concern. Knowledge of both protective and negative risk factors is essential for a better understanding of this heterogenous disease. We undertook a review of the recent literature and evaluated the relationship between obesity mediators and breast cancer development depending on menopausal status. Excess weight is now pandemic and has replaced tobacco as the main lifestyle-related risk factor for premature death. Although the prevalence of obesity/overweight has increased globally over the last 50 years, the potential harm attributable to excess fat has generally been underestimated. The relationship between overweight/obesity, breast cancer and overall risk appears to be highly dependent on menopausal status. Thus, obesity increases the risk of breast cancer in postmenopausal women but, conversely, it appears to be protective in premenopausal women. We evaluate the role of different clinical factors potentially involved in this seemingly contradictory relationship, including estrogen, mammogram density, adipokines, insulin-signaling pathway activation, and inflammatory status. A key focus of this review is to better understand the impact of body mass index and menopausal status on these clinical factors and, hence, provide some clarity into the inter-relationships involved in this controversial issue.
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Affiliation(s)
- Laura García-Estévez
- Breast Cancer Department, MD Anderson Cancer Center, Madrid, Spain.,Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain
| | - Javier Cortés
- International Breast Cancer Center (IBCC), Barcelona, Spain.,Medical Scientia Innovation Research (MedSIR), Barcelona, Spain.,Vall d'Hebron Institute of Oncology, Barcelona, Spain
| | - Silvia Pérez
- Breast Cancer Department, MD Anderson Cancer Center, Madrid, Spain
| | - Isabel Calvo
- Breast Cancer Department, MD Anderson Cancer Center, Madrid, Spain
| | - Isabel Gallegos
- Breast Cancer Department, MD Anderson Cancer Center, Madrid, Spain
| | - Gema Moreno-Bueno
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.,Biochemistry Department, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM), IdiPaz, & Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.,MD Anderson International Foundation, Madrid, Spain
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28
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Ranaweera SS, Dissanayake CY, Natraj P, Lee YJ, Han CH. Anti-inflammatory effect of sulforaphane on LPS-stimulated RAW 264.7 cells and ob/ob mice. J Vet Sci 2021; 21:e91. [PMID: 33263238 PMCID: PMC7710464 DOI: 10.4142/jvs.2020.21.e91] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Revised: 10/22/2020] [Accepted: 10/28/2020] [Indexed: 12/28/2022] Open
Abstract
Background Sulforaphane (SFN) is an isothiocyanate compound present in cruciferous vegetables. Although the anti-inflammatory effects of SFN have been reported, the precise mechanism related to the inflammatory genes is poorly understood. Objectives This study examined the relationship between the anti-inflammatory effects of SFN and the differential gene expression pattern in SFN treated ob/ob mice. Methods Nitric oxide (NO) level was measured using a Griess assay. The inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression levels were analyzed by Western blot analysis. Pro-inflammatory cytokines (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, and IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). RNA sequencing analysis was performed to evaluate the differential gene expression in the liver of ob/ob mice. Results The SFN treatment significantly attenuated the iNOS and COX-2 expression levels and inhibited NO, TNF-α, IL-1β, and IL-6 production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. RNA sequencing analysis showed that the expression levels of 28 genes related to inflammation were up-regulated (> 2-fold), and six genes were down-regulated (< 0.6-fold) in the control ob/ob mice compared to normal mice. In contrast, the gene expression levels were restored to the normal level by SFN. The protein-protein interaction (PPI) network showed that chemokine ligand (Cxcl14, Ccl1, Ccl3, Ccl4, Ccl17) and chemokine receptor (Ccr3, Cxcr1, Ccr10) were located in close proximity and formed a “functional cluster” in the middle of the network. Conclusions The overall results suggest that SFN has a potent anti-inflammatory effect by normalizing the expression levels of the genes related to inflammation that were perturbed in ob/ob mice.
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Affiliation(s)
| | | | - Premkumar Natraj
- College of Veterinary Medicine, Jeju National University, Jeju 63243, Korea
| | - Young Jae Lee
- College of Veterinary Medicine, Jeju National University, Jeju 63243, Korea
| | - Chang Hoon Han
- College of Veterinary Medicine, Jeju National University, Jeju 63243, Korea.
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29
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Ying L, Zhang M, Ma X, Si Y, Li X, Su J, Yin J, Bao Y. Macrophage LAMTOR1 Deficiency Prevents Dietary Obesity and Insulin Resistance Through Inflammation-Induced Energy Expenditure. Front Cell Dev Biol 2021; 9:672032. [PMID: 34095141 PMCID: PMC8173123 DOI: 10.3389/fcell.2021.672032] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 04/26/2021] [Indexed: 12/31/2022] Open
Abstract
Here, we studied the metabolic function of LAMTOR1 from macrophages using LAMTOR1 macrophage-specific knockout (MKO) mice. LAMTOR1 MKO mice showed resistance to high-fat diet (HFD)-induced obesity, lipid steatosis, and glucose metabolic disorders, with elevated levels of pro-inflammatory cytokines. The energy expenditure, oxygen consumption, and CO2 production increased significantly in HFD-fed MKO vs. wild-type (WT) mice. HE and immunohistochemistry staining showed a remarkable CD68+ Kupffer cell accumulation in the liver. Additionally, flow cytometry revealed that the proportion of macrophages and monocytes increased significantly in the liver of MKO mice. Of note, these macrophages were probably derived from the bone marrow since the proportion of CD11b+ cells as well as the proliferative activity was also increased in the context of femoral bone marrow cells. In addition, the Kupffer cells of both WT and KO mice were double-positive for the M1 (CD86) and M2 (CD206) markers. However, the expression of both M1 and M2 macrophage-related genes was increased in the liver of HFD-fed KO mice. Murine primary hepatocytes and Kupffer cells were further isolated and incubated with oleic acid for 24 h. The glucose output of primary hepatocytes from MKO mice was not affected. However, decreased lipid tolerance was observed in LAMTOR1-deficient Kupffer cells. Overall, our results suggest that LAMTOR1 deficiency in macrophages prevents obesity and metabolic disorders via the accumulation of Kupffer cells in the liver and the consequent hyper-inflammation and increased energy expenditure. Therefore, our results provide a new perspective for macrophage-derived LAMTOR1 in the context of systemic metabolism.
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Affiliation(s)
- Lingwen Ying
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, China
| | - Mingliang Zhang
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, China
| | - Xiaojing Ma
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, China
| | - Yiming Si
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, China
| | - Xiaoya Li
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, China
| | - Jiaorong Su
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, China
| | - Jun Yin
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, China.,Department of Endocrinology and Metabolism, Shanghai Eighth People's Hospital, Shanghai, China
| | - Yuqian Bao
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, China
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30
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Prestwood TR, Asgariroozbehani R, Wu S, Agarwal SM, Logan RW, Ballon JS, Hahn MK, Freyberg Z. Roles of inflammation in intrinsic pathophysiology and antipsychotic drug-induced metabolic disturbances of schizophrenia. Behav Brain Res 2021; 402:113101. [PMID: 33453341 PMCID: PMC7882027 DOI: 10.1016/j.bbr.2020.113101] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 12/10/2020] [Accepted: 12/27/2020] [Indexed: 02/06/2023]
Abstract
Schizophrenia is a debilitating psychiatric illness that remains poorly understood. While the bulk of symptomatology has classically been associated with disrupted brain functioning, accumulating evidence demonstrates that schizophrenia is characterized by systemic inflammation and disturbances in metabolism. Indeed, metabolic disease is a major determinant of the high mortality rate associated with schizophrenia. Antipsychotic drugs (APDs) have revolutionized management of psychosis, making it possible to rapidly control psychotic symptoms. This has ultimately reduced relapse rates of psychotic episodes and improved overall quality of life for people with schizophrenia. However, long-term APD use has also been associated with significant metabolic disturbances including weight gain, dysglycemia, and worsening of the underlying cardiometabolic disease intrinsic to schizophrenia. While the mechanisms for these intrinsic and medication-induced metabolic effects remain unclear, inflammation appears to play a key role. Here, we review the evidence for roles of inflammatory mechanisms in the disease features of schizophrenia and how these mechanisms interact with APD treatment. We also discuss the effects of common inflammatory mediators on metabolic disease. Then, we review the evidence of intrinsic and APD-mediated effects on systemic inflammation in schizophrenia. Finally, we speculate about possible treatment strategies. Developing an improved understanding of inflammatory processes in schizophrenia may therefore introduce new, more effective options for treating not only schizophrenia but also primary metabolic disorders.
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Affiliation(s)
- Tyler R Prestwood
- Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA
| | - Roshanak Asgariroozbehani
- Centre for Addiction and Mental Health, Toronto, ON, Canada; Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Sally Wu
- Centre for Addiction and Mental Health, Toronto, ON, Canada; Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Sri Mahavir Agarwal
- Centre for Addiction and Mental Health, Toronto, ON, Canada; Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Banting and Best Diabetes Centre (BBDC), University of Toronto, Toronto, ON, Canada
| | - Ryan W Logan
- Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA; Center for Systems Neurogenetics of Addiction, The Jackson Laboratory, Bar Harbor, ME, USA
| | - Jacob S Ballon
- Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA
| | - Margaret K Hahn
- Centre for Addiction and Mental Health, Toronto, ON, Canada; Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Banting and Best Diabetes Centre (BBDC), University of Toronto, Toronto, ON, Canada.
| | - Zachary Freyberg
- Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA; Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA, USA.
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31
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Kim DH, Chun SY, Lee E, Kim B, Yoon B, Gil H, Han MH, Ha YS, Lee JN, Kwon TG, Kim BS, Jang BI. IL-10 Deficiency Aggravates Renal Inflammation, Fibrosis and Functional Failure in High-Fat Dieted Obese Mice. Tissue Eng Regen Med 2021; 18:399-410. [PMID: 33547567 PMCID: PMC8169746 DOI: 10.1007/s13770-020-00328-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2020] [Revised: 12/02/2020] [Accepted: 12/03/2020] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND: High-fat diet-induced obesity is one of the major cause of chronic renal failure. This obesity-related renal failure is mainly caused by inflammatory processes. However, the role of the major anti-inflammatory cytokine interleukin (IL)-10 has not been researched intensively. METHODS: To evaluate the effect of IL-10 deficiency on obesity-related renal failure, the in vivo study was carried with four animal groups; (1) Low-fat dieted C57BL/6 mice, (2) Low-fat dieted IL-10 knockout (KO) mice, (3) High‐fat dieted C57BL/6 mice and (4) High‐fat dieted IL-10 KO mice group. The analysis was carried with blood/urine chemistry, H&E, Oil-Red-O, periodic acid-Schiff and Masson’s trichrome staining immunohistochemistry and real-time PCR methods. RESULTS: At week 12, high‐fat dieted IL-10 KO mice showed 1) severe lipid accumulation in kidneys, cholesterol elevation (in total, serum kidney) and low-density lipoprotein increasion through the SCAP-SREBP2-LDLr pathway; (2) serious histopathologic alterations showing glomerulosclerosis, tubulointerstitial fibrosis and immune cell infiltration; (3) increased pro‐inflammatory cytokines and chemokines expression; (4) enhanced renal fibrosis; and (5) serious functional failure with high serum creatinine and BUN and proteinuria excretion compared to other groups. CONCLUSION: IL-10 deficiency aggravates renal inflammation, fibrosis and functional failure in high-fat dieted obese mice, thus IL-10 therapy could be applied to obesity-related chronic renal failure.
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Affiliation(s)
- Dae Hwan Kim
- Department of Laboratory Animal Research Support Team, Yeungnam University Medical Center, Daegu, 42415, Republic of Korea
| | - So Young Chun
- BioMedical Research Institute, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea
| | - EunHye Lee
- Department of Pathology, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea
| | - Bomi Kim
- BioMedical Research Institute, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea
| | - BoHyun Yoon
- BioMedical Research Institute, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea
| | - Haejung Gil
- BioMedical Research Institute, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea
| | - Man-Hoon Han
- Department of Pathology, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea
| | - Yun-Sok Ha
- Department of Urology, Kyungpook National University Chilgok Hospital, Daegu, Korea
| | - Jun Nyung Lee
- Department of Urology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Tae Gyun Kwon
- Department of Urology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Bum Soo Kim
- Department of Urology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
| | - Byung Ik Jang
- Department of Internal Medicine, School of Medicine, Yeungnam University, Daegu, Republic of Korea.
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Basolo A, Ando T, Chang DC, Hollstein T, Krakoff J, Piaggi P, Votruba S. Reduced Albumin Concentration Predicts Weight Gain and Higher Ad Libitum Energy Intake in Humans. Front Endocrinol (Lausanne) 2021; 12:642568. [PMID: 33776937 PMCID: PMC7991842 DOI: 10.3389/fendo.2021.642568] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Accepted: 01/25/2021] [Indexed: 12/01/2022] Open
Abstract
OBJECTIVE Circulating albumin is negatively associated with adiposity but whether it is associated with increased energy intake, lower energy expenditure or weight gain has not been examined. METHODS In study 1 (n=238; 146 men), we evaluated whether fasting albumin concentration was associated with 24-h energy expenditure and ad libitum energy intake. In study 2 (n=325;167 men), we evaluated the association between plasma albumin and change in weight and body composition. RESULTS After adjustment for known determinants of energy intake lower plasma albumin concentration was associated with greater total daily energy intake (β= 89.8 kcal/day per 0.1 g/dl difference in plasma albumin, p=0.0047). No associations were observed between plasma albumin concentrations and 24-h energy expenditure or 24-h respiratory quotient (p>0.2). Over 6 years, volunteers gained on average 7.5 ± 11.7 kg (p<0.0001). Lower albumin concentrations were associated with greater weight [β=3.53 kg, p=0.039 (adjusted for age, sex, follow up time), CI 0.16 to 6.21 per 1 g/dl difference albumin concentration] and fat mass (β=2.3 kg, p=0.022), respectively, but not with changes in fat free mass (p=0.06). CONCLUSIONS Lower albumin concentrations were associated with increased ad libitum food intake and weight gain, indicating albumin as a marker of energy intake regulation. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, identifiers NCT00340132, NCT00342732.
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Affiliation(s)
- Alessio Basolo
- Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, United States
- Unit of Endocrinology, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy
- *Correspondence: Alessio Basolo,
| | - Takafumi Ando
- Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, United States
- Japan Society for the Promotion of Science, Tokyo, Japan
| | - Douglas C. Chang
- Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, United States
| | - Tim Hollstein
- Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, United States
| | - Jonathan Krakoff
- Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, United States
| | - Paolo Piaggi
- Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, United States
- Department of Information Engineering, University of Pisa, Pisa, Italy
| | - Susanne Votruba
- Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, United States
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Hwang J, Yoo JA, Yoon H, Han T, Yoon J, An S, Cho JY, Lee J. The Role of Leptin in the Association between Obesity and Psoriasis. Biomol Ther (Seoul) 2021; 29:11-21. [PMID: 32690821 PMCID: PMC7771847 DOI: 10.4062/biomolther.2020.054] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 06/17/2020] [Accepted: 07/03/2020] [Indexed: 12/11/2022] Open
Abstract
Adipose tissue secretes many adipokines which contribute to various metabolic processes, such as blood pressure, glucose homeostasis, inflammation and angiogenesis. The biology of adipose tissue in an obese individual is abnormally altered in a manner that increases the body’s vulnerability to immune diseases, such as psoriasis. Psoriasis is considered a chronic inflammatory skin disease which is closely associated with being overweight and obese. Additionally, secretion of leptin, a type of adipokine, increases dependently on adipose cell size and adipose accumulation. Likewise, high leptin levels also aggravate obesity via development of leptin resistance, suggesting that leptin and obesity are closely related. Leptin induction in psoriatic patients is mainly driven by the interleukin (IL)-23/helper T (Th) 17 axis pathway. Furthermore, leptin can have an effect on various types of immune cells such as T cells and dendritic cells. Here, we discuss the relationship between obesity and leptin expression as well as the linkage between effect of leptin on immune cells and psoriasis progression.
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Affiliation(s)
- Jaehyeon Hwang
- Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Ju Ah Yoo
- Molecular Dermatology Laboratory, Department of Integrative Biotechnology & Biocosmetics Research Center, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Hyungkee Yoon
- Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Taekyung Han
- Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Jongchan Yoon
- Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Seoljun An
- Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Jae Youl Cho
- Molecular Immunology Laboratory, Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Jongsung Lee
- Molecular Dermatology Laboratory, Department of Integrative Biotechnology & Biocosmetics Research Center, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
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Lee SH, Choi NH, Koh IU, Kim BJ, Lee S, Kim SC, Choi SS. Putative positive role of inflammatory genes in fat deposition supported by altered gene expression in purified human adipocytes and preadipocytes from lean and obese adipose tissues. J Transl Med 2020; 18:433. [PMID: 33183332 PMCID: PMC7664034 DOI: 10.1186/s12967-020-02611-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 11/05/2020] [Indexed: 01/08/2023] Open
Abstract
Background Obesity is a chronic low-grade inflammatory disease that is generally characterized by enhanced inflammation in obese adipose tissue (AT). Here, we investigated alterations in gene expression between lean and obese conditions using mRNA-Seq data derived from human purified adipocytes (ACs) and preadipocytes (preACs). Results Total mRNA-seq data were generated with 27 AC and 21 preAC samples purified from human visceral AT collected during resection surgery in cancer patients, where the samples were classified into lean and obese categories by BMI > 25 kg/m2. We defined four classes of differentially expressed genes (DEGs) by comparing gene expression between (1) lean and obese ACs, (2) lean and obese preACs, (3) lean ACs and lean preACs, and 4) obese ACs and obese preACs. Based on an analysis of comparison 1, numerous canonical obesity-related genes, particularly inflammatory genes including IL-6, TNF-α and IL-1β, i.e., the genes that are expected to be upregulated in obesity conditions, were found to be expressed at significantly lower levels in obese ACs than in lean ACs. In contrast, some inflammatory genes were found to be expressed at higher levels in obese preACs than lean preACs in the analysis of comparison 2. The analysis of comparisons 3 and 4 showed that inflammatory gene classes were expressed at higher levels in differentiated ACs than undifferentiated preACs under both lean and obese conditions; however, the degree of upregulation was significantly greater for lean than for obese conditions. We validated our observations using previously published microarray transcriptome data deposited in the GEO database (GSE80654). Conclusions Taken together, our analyses suggest that inflammatory genes are expressed at lower levels in obese ACs than in lean ACs because lean adipogenesis involves even greater enhancement of inflammatory responses than does obese adipogenesis.
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Affiliation(s)
- Sang-Hyeop Lee
- Division of Biomedical Convergence, College of Biomedical Science, Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon, Gangwon-do, 24341, Korea
| | - Nak-Hyeon Choi
- Division of Genome Science, Department of Precision Medicine, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju-si, Chuncheongbuk-do, 28159, Korea
| | - In-Uk Koh
- Division of Genome Science, Department of Precision Medicine, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju-si, Chuncheongbuk-do, 28159, Korea
| | - Bong-Jo Kim
- Division of Genome Science, Department of Precision Medicine, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju-si, Chuncheongbuk-do, 28159, Korea
| | - Song Lee
- Asan Institute for Life Science, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Song-Cheol Kim
- Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Sun Shim Choi
- Division of Biomedical Convergence, College of Biomedical Science, Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon, Gangwon-do, 24341, Korea.
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Song SY, Kim IS, Koppula S, Park JY, Kim BW, Yoon SH, Choi DK. 2-Hydroxy-4-Methylbenzoic Anhydride Inhibits Neuroinflammation in Cellular and Experimental Animal Models of Parkinson's Disease. Int J Mol Sci 2020; 21:ijms21218195. [PMID: 33147699 PMCID: PMC7662568 DOI: 10.3390/ijms21218195] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Revised: 10/21/2020] [Accepted: 10/26/2020] [Indexed: 12/12/2022] Open
Abstract
Microglia-mediated neuroinflammation is one of the key mechanisms involved in acute brain injury and chronic neurodegeneration. This study investigated the inhibitory effects of 2-hydroxy-4-methylbenzoic anhydride (HMA), a novel synthetic derivative of HTB (3-hydroxy-4-trifluoromethylbenzoic acid) on neuroinflammation and underlying mechanisms in activated microglia in vitro and an in vivo mouse model of Parkinson’s disease (PD). In vitro studies revealed that HMA significantly inhibited lipopolysaccharide (LPS)-stimulated excessive release of nitric oxide (NO) in a concentration dependent manner. In addition, HMA significantly suppressed both inducible NO synthase and cyclooxygenase-2 (COX-2) at the mRNA and protein levels in LPS-stimulated BV-2 microglia cells. Moreover, HMA significantly inhibited the proinflammatory cytokines such as interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha in LPS-stimulated BV-2 microglial cells. Furthermore, mechanistic studies ensured that the potent anti-neuroinflammatory effects of HMA (0.1, 1.0, and 10 μM) were mediated by phosphorylation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) in LPS-stimulated BV-2 cells. In vivo evaluations revealed that intraperitoneal administration of potent neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 20 mg/kg, four times a 1 day) in mice resulted in activation of microglia in the brain in association with severe behavioral deficits as assessed using a pole test. However, prevention of microglial activation and attenuation of Parkinson’s disease (PD)-like behavioral changes was obtained by oral administration of HMA (30 mg/kg) for 14 days. Considering the overall results, our study showed that HMA exhibited strong anti-neuroinflammatory effects at lower concentrations than its parent compound. Further work is warranted in other animal and genetic models of PD for evaluating the efficacy of HMA to develop a potential therapeutic agent in the treatment of microglia-mediated neuroinflammatory disorders, including PD.
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Affiliation(s)
- Soo-Yeol Song
- Department of Biotechnology, Konkuk University, Chungju 380-701, Korea; (S.-Y.S.); (I.-S.K.); (S.K.); (B.-W.K.)
| | - In-Su Kim
- Department of Biotechnology, Konkuk University, Chungju 380-701, Korea; (S.-Y.S.); (I.-S.K.); (S.K.); (B.-W.K.)
| | - Sushruta Koppula
- Department of Biotechnology, Konkuk University, Chungju 380-701, Korea; (S.-Y.S.); (I.-S.K.); (S.K.); (B.-W.K.)
| | - Ju-Young Park
- Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Korea; (J.-Y.P.); (S.-H.Y.)
| | - Byung-Wook Kim
- Department of Biotechnology, Konkuk University, Chungju 380-701, Korea; (S.-Y.S.); (I.-S.K.); (S.K.); (B.-W.K.)
| | - Sung-Hwa Yoon
- Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Korea; (J.-Y.P.); (S.-H.Y.)
| | - Dong-Kug Choi
- Department of Biotechnology, Konkuk University, Chungju 380-701, Korea; (S.-Y.S.); (I.-S.K.); (S.K.); (B.-W.K.)
- Correspondence: ; Tel.: +82-43-840-3616
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Single cell sequencing unraveling genetic basis of severe COVID19 in obesity. ACTA ACUST UNITED AC 2020; 20:100303. [PMID: 32995660 PMCID: PMC7513689 DOI: 10.1016/j.obmed.2020.100303] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 09/20/2020] [Accepted: 09/20/2020] [Indexed: 12/15/2022]
Abstract
COVID-19 has shown a substantial variation in the rate and severity by which it impacts different demographic groups. Specifically, it has shown a predilection towards obese patients as well as well as other vulnerable groups including predilection of males over females, old age over young age and black races over Caucasian ones. Single cell sequencing studies have highlighted the role of cell polarity and the co-expression of proteases, such as Furin, along with ACE2 in the genesis of coronavirus disease rather than exclusively link tissue involvement with ACE2 levels thought previously. It has also forged a connection between the genetic and immune cellular mechanisms underlying COVID infection and the inflammatory state of obese patients, offering a more accurate explanation as to why obese patients are at increased risk of poor COVID outcomes. These commonalities encompass macrophage phenotype switching, genetic expression switching, and overexpression of the pro-inflammatory cytokines, depletion of the regulatory cytokines, in situ T cell proliferation, and T cell exhaustion. These findings demonstrate the necessity of single cell sequencing as a rapid means to identify and treat those who are most likely to need hospital admission and intensive care, in the hopes of precision medicine. Furthermore, this study underlines the use of immune modulators such as Leptin sensitizers, rather than immune suppressors as anti-inflammation therapies to switch the inflammatory response from a drastic immunological type 1 response to a beneficial type 2 effective one.
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Endometrial Cancer as a Metabolic Disease with Dysregulated PI3K Signaling: Shedding Light on Novel Therapeutic Strategies. Int J Mol Sci 2020; 21:ijms21176073. [PMID: 32842547 PMCID: PMC7504460 DOI: 10.3390/ijms21176073] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Revised: 08/21/2020] [Accepted: 08/21/2020] [Indexed: 12/15/2022] Open
Abstract
Endometrial cancer (EC) is one of the most common malignancies of the female reproductive organs. The most characteristic feature of EC is the frequent association with metabolic disorders. However, the components of these disorders that are involved in carcinogenesis remain unclear. Accumulating epidemiological studies have clearly revealed that hyperinsulinemia, which accompanies these disorders, plays central roles in the development of EC via the insulin-phosphoinositide 3 kinase (PI3K) signaling pathway as a metabolic driver. Recent comprehensive genomic analyses showed that over 90% of ECs have genomic alterations in this pathway, resulting in enhanced insulin signaling and production of optimal tumor microenvironments (TMEs). Targeting PI3K signaling is therefore an attractive treatment strategy. Several clinical trials for recurrent or advanced ECs have been attempted using PI3K-serine/threonine kinase (AKT) inhibitors. However, these agents exhibited far lower efficacy than expected, possibly due to activation of alternative pathways that compensate for the PIK3-AKT pathway and allow tumor growth, or due to adaptive mechanisms including the insulin feedback pathway that limits the efficacy of agents. Overcoming these responses with careful management of insulin levels is key to successful treatment. Further interest in specific TMEs via the insulin PI3K-pathway in obese women will provide insight into not only novel therapeutic strategies but also preventive strategies against EC.
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Alipour M, Rostami H, Parastouei K. Association between inflammatory obesity phenotypes, FTO-rs9939609, and cardiovascular risk factors in patients with type 2 diabetes. JOURNAL OF RESEARCH IN MEDICAL SCIENCES 2020; 25:46. [PMID: 32765616 PMCID: PMC7377118 DOI: 10.4103/jrms.jrms_429_19] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/03/2019] [Revised: 10/08/2019] [Accepted: 02/17/2020] [Indexed: 12/17/2022]
Abstract
Background The role of inflammatory states in cardiometabolic risks among patients with type 2 diabetes mellitus (T2DM) with similar degrees of obesity is unknown. The study aimed to compare cardiometabolic risk factors in inflammatory obesity phenotypes with regard to the role of the FTO rs9939609 gene polymorphism. Materials and Methods This study was performed on 155 patients with T2DM (77 men and 78 women) in Ahvaz, Iran. Participants were grouped into four groups based on the presence of obesity and inflammation (high-sensitivity C-reactive protein ≥3.9 mg/L): low inflammatory normal weight (LINW), high inflammatory normal weight (HINW), low inflammatory obese (LIO), and high inflammatory obese (HIO). The genotypes of FTO rs9939609, including homozygous carriers of the FTO risk allele (AA), heterozygous carriers (AT), and carrying no risk allele (TT), were studied. The cardiometabolic risk factors, including anthropometric status, hypertension, lipid and glycemic profile, and inflammatory markers, were evaluated. The waist-hip ratio (WHR), mean arterial pressure (MAP), and atherogenic index of plasma (AIP) were calculated. Results The patients in inflammatory groups (HINW and HIO) have significantly higher levels in AIP when compared to inflammatory healthy groups (LINW and LIO). No significant differences between any of the four group means were detected in WHR, blood pressure, MAP, glycemic status (fasting blood sugar and insulin), homeostatic model assessment, lipid profile (triglyceride, very low-density lipoprotein, high-density lipoprotein, low-density lipoprotein, and cholesterol), interleukin-6, and total antioxidant capacity. The most frequent of high-risk genotype (AA) of FTO rs9939609 was in HIO, LIO, HINW, and LINW. Conclusion T2DM patients with inflammatory condition have similar degree of increased atherogenic risk irrespective of obesity. The obesity-risk genotype AA of FTO gene was associated with an increased risk for inflammatory obesity in T2DM patients.
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Affiliation(s)
- Meysam Alipour
- Health Research Center, Life Style Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Hosein Rostami
- Health Research Center, Life Style Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Karim Parastouei
- Health Research Center, Life Style Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
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Xia QS, Lu FE, Wu F, Huang ZY, Dong H, Xu LJ, Gong J. New role for ceramide in hypoxia and insulin resistance. World J Gastroenterol 2020; 26:2177-2186. [PMID: 32476784 PMCID: PMC7235208 DOI: 10.3748/wjg.v26.i18.2177] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 04/08/2020] [Accepted: 04/24/2020] [Indexed: 02/06/2023] Open
Abstract
Ceramides are significant metabolic products of sphingolipids in lipid metabolism and are associated with insulin resistance and hepatic steatosis. In chronic inflammatory pathological conditions, hypoxia occurs, the metabolism of ceramide changes, and insulin resistance arises. Hypoxia-inducible factors (HIFs) are a family of transcription factors activated by hypoxia. In hypoxic adipocytes, HIF-1α upregulates pla2g16 (a novel HIF-1α target gene) gene expression to activate the NLRP3 inflammasome pathway and stimulate insulin resistance, and adipocyte-specific Hif1a knockout can ameliorate homocysteine-induced insulin resistance in mice. The study on the HIF-2α—NEU3—ceramide pathway also reveals the role of ceramide in hypoxia and insulin resistance in obese mice. Under obesity-induced intestinal hypoxia, HIF-2α increases the production of ceramide by promoting the expression of the gene Neu3 encoding sialidase 3, which is a key enzyme in ceramide synthesis, resulting in insulin resistance in high-fat diet-induced obese mice. Moreover, genetic and pathophysiologic inhibition of the HIF-2α—NEU3—ceramide pathway can alleviate insulin resistance, suggesting that these could be potential drug targets for the treatment of metabolic diseases. Herein, the effects of hypoxia and ceramide, especially in the intestine, on metabolic diseases are summarized.
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Affiliation(s)
- Qing-Song Xia
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Fu-Er Lu
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Fan Wu
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Zhao-Yi Huang
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Hui Dong
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Li-Jun Xu
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Jing Gong
- Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
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Lacerda DR, Soares DD, Costa KA, Nunes-Silva A, Rodrigues DF, Sabino JL, Silveira ALM, Pinho V, Vieira ÉLM, Menezes GB, Antunes MM, Teixeira MM, Ferreira AVM. Mechanisms underlying fat pad remodeling induced by fasting: role of PAF receptor. Nutrition 2020; 71:110616. [DOI: 10.1016/j.nut.2019.110616] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Revised: 08/24/2019] [Accepted: 10/05/2019] [Indexed: 01/09/2023]
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Phillips CL, Grayson BE. The immune remodel: Weight loss-mediated inflammatory changes to obesity. Exp Biol Med (Maywood) 2020; 245:109-121. [PMID: 31955604 PMCID: PMC7016415 DOI: 10.1177/1535370219900185] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Obesity is an escalating world problem that contributes to the complexity and cost of treatment of metabolic disorders. Obesity is the result of increased storage of energy in the form of adipose tissue, reducing the quality of daily life, and interfering with longevity. Obesity is also a chronic, low-grade inflammatory disorder. The inflammatory processes affect many organ systems with expanded numbers of immune cells and increased cytokine production. Long-term weight loss is difficult to achieve and maintain. Lifestyle modifications, pharmacologic treatments, and surgical methods are increasingly utilized to ameliorate excess body weight and the comorbidities of obesity, such as diabetes, cardiovascular disease, dyslipidemia, and cancers. Weight loss is also touted to reduce inflammation. Here we review the current literature on human obesity-related systemic and local changes to the immune system and circulating inflammatory mediators. Further, we consider the impact of weight loss to reduce the burden of inflammation, bearing in mind the different methods of weight loss—behavioral change vs. surgical intervention.
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Affiliation(s)
- Charles L Phillips
- Program in Pathology, University of Mississippi Medical Center, Jackson, MS 39216, USA
| | - Bernadette E Grayson
- Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, MS 39216, USA
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Abstract
In the present study, the performance of anthropometric parameters, lipid and glucose indexes, and the combination of anthropometric parameters with the TyG (triglycerides × fasting plasma glucose) metabolic index, was compared in detecting insulin resistance (IR) to evaluate the optimal cut-off points in nondiabetic Chinese individuals. A total of 1067 nondiabetics underwent oral glucose tolerance test, blood lipid, and fasting insulin measurements. The clinical usefulness of various parameters- body mass index (BMI), waist circumference (WC), TyG, triglycerides/ high density lipoprotein cholesterol ratio, and TyG with adiposity status (TyG-BMI [TyG × BMI] and TyG-WC)-was analyzed to identify IR. Spearman correlation and receiver-operating characteristic curve analyses were used to compare the predictive efficacy of different indicators. All indicators showed a positive correlation with IR in both normal glucose and all subjects. However, the correlation between BMI and homeostasis model assessment of IR index was higher than other indicators as assessed by Spearman correlation test (P < .05). Furthermore, BMI and TyG-BMI were better indicators than others as determined by comparing the area under the receiver-operating characteristics curves (P < .05) in detecting IR. BMI is a simple and accurate measure for detecting IR in Chinese subjects. The 27 kg/m threshold was the optimal BMI cut-off point for detecting IR in both normal glucose and all glucose categories subjects.
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Affiliation(s)
- Xiu Tuo
- Department of Endocrinology, Beijing Tongren Hospital
- Beijing key Laboratory of Diabetes Prevention and Research, Dong Jiao Min Xiang
- Department of Internal Medicine, Beijing Sijiqing Hospital, Beijing, China
| | - Jing Yuan
- Department of Endocrinology, Beijing Tongren Hospital
- Beijing key Laboratory of Diabetes Prevention and Research, Dong Jiao Min Xiang
| | - Xu-Hong Wang
- Department of Endocrinology, Beijing Luhe hospital, Capital Medical University
- Beijing key Laboratory of Diabetes Prevention and Research, Dong Jiao Min Xiang
| | - Zhong Xin
- Department of Endocrinology, Beijing Tongren Hospital
- Beijing key Laboratory of Diabetes Prevention and Research, Dong Jiao Min Xiang
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Ren L. Protective effect of ganoderic acid against the streptozotocin induced diabetes, inflammation, hyperlipidemia and microbiota imbalance in diabetic rats. Saudi J Biol Sci 2019; 26:1961-1972. [PMID: 31889779 PMCID: PMC6923438 DOI: 10.1016/j.sjbs.2019.07.005] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 06/15/2019] [Accepted: 07/05/2019] [Indexed: 01/03/2023] Open
Abstract
Diabetes mellitus (DM) is a metabolic disorder with numerous symptoms categorized via serves hyperglycemia effect along with altered fat, protein and carbohydrate metabolism mainly resultant from defects in insulin action/secretion or both. The aim of the current experimental study was to comfort the neuroprotective effect of ganoderic acid against the streptozotocin (STZ)-induced type I diabetes mellitus in mice and explore the underlying mechanism. Differentiation of 3T3-L1 preadipocytes effect; hepatic and glucose consumption effect of ganoderic acid was estimated on HepG2 cell lines and peroxisome proliferator-activated receptor (PPAR). FFA content was estimated in adipose and hepatic tissues. Ganoderic acid induced the 3T3-L1 preadipocytes differentiation. The mRNA expression of PPAR was increased in the high glucose-treated group in HepG2 and ganoderic acid treatment down-regulated the mRNA expression of PPAR. Ganoderic acid exhibited the inhibitory effect of α-glucosidase and α-amylase. Ganoderic acid demonstrated the reduced blood glucose and increase insulin level and also reduced the free fatty in hepatic and adipose tissue. Histopathological study showed the enhancement of β-cells in ganoderic acid-treated mice. Finally, their prebiotic effects on gut microbiota were illustrated via enhancing the population of diabetes resistant bacteria and also reducing the quantity of diabetes sensitive bacteria. Ganoderic acid attenuated STZ induced T1DM in mice via inflammatory pathways.
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Fujita N, Goto N, Nakamura T, Nino W, Ono T, Nishijo H, Urakawa S. Hyperbaric Normoxia Improved Glucose Metabolism and Decreased Inflammation in Obese Diabetic Rat. J Diabetes Res 2019; 2019:2694215. [PMID: 31828157 PMCID: PMC6885850 DOI: 10.1155/2019/2694215] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Revised: 10/09/2019] [Accepted: 11/02/2019] [Indexed: 12/14/2022] Open
Abstract
Hyperbaric treatment improves hyperglycemia and hyperinsulinemia in type 2 diabetes associated with obesity. However, its mode of action is unknown. The purpose of the present study was to investigate the influences of regular hyperbaric treatment with normal air at 1.3 atmospheres absolute (ATA) on glucose tolerance in type 2 diabetes with obesity. The focus was directed on inflammatory cytokines in the adipose tissue and skeletal muscle. Otsuka Long-Evans Tokushima Fatty (OLETF) rats were used as models of type 2 diabetes with obesity and Long-Evans Tokushima Otsuka (LETO) rats served as healthy controls. The rats were randomly assigned to untreated or hyperbaric treatment groups exposed to 1.3 ATA for 8 h d-1 and 5 d wk-1 for 16 wks. Glucose levels were significantly higher in the diabetic than in the healthy control rats. Nevertheless, glucose levels at 30 and 60 min after glucose administration were significantly lower in the diabetic rats treated with 1.3 ATA than in the untreated diabetic rats. Insulin levels at fasting and 120 min after glucose administration were significantly lower in the diabetic rats treated with 1.3 ATA than in the untreated diabetic rats. Hyperbaric treatment also increased interleukin-10 (IL-10) expression in the skeletal muscle and decreased tumor necrosis factor α (TNFα) expression in adipose tissue. These results suggested that TNFα downregulation and IL-10 upregulation in diabetic rats subjected to hyperbaric treatment participate in the crosstalk between the adipose and skeletal muscle tissues and improve glucose intolerance.
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Affiliation(s)
- Naoto Fujita
- Department of Musculoskeletal Functional Research and Regeneration, Graduate School of Biomedicine and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan
| | - Natsuki Goto
- Department of Musculoskeletal Functional Research and Regeneration, Graduate School of Biomedicine and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan
| | - Tomoya Nakamura
- Department of Musculoskeletal Functional Research and Regeneration, Graduate School of Biomedicine and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan
| | - Wataru Nino
- Department of Musculoskeletal Functional Research and Regeneration, Graduate School of Biomedicine and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan
| | - Taketoshi Ono
- System Emotional Science, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan
| | - Hisao Nishijo
- System Emotional Science, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan
| | - Susumu Urakawa
- Department of Musculoskeletal Functional Research and Regeneration, Graduate School of Biomedicine and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan
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Chen LS, Li YY, Chen H, Liu BW, Wang DW, Zhao YH. Polyglycolic acid sutures embedded in abdominal acupoints for treatment of simple obesity in adults: a randomized control trial. Chin Med 2019; 14:32. [PMID: 31548850 PMCID: PMC6749682 DOI: 10.1186/s13020-019-0258-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Accepted: 09/11/2019] [Indexed: 12/15/2022] Open
Abstract
Background Acupoint catgut embedding therapy characterized by acupoint, needle and catgut are superior to traditional acupuncture, due to exerting more comprehensive therapeutic efficacy. However, it is still deficient in clinical evidence for polyglycolic acid sutures, a novel biodegradable material instead of catgut, embedded for the treatment of simple obesity. In our study, we investigate the efficacy and related mechanism of polyglycolic acid sutures embedded in abdominal acupoints on simple obese persons by a randomized control trial. Methods A total of 51 eligible participators were randomly allocated to a polyglycolic acid sutures embedding therapy (PASET) group (n = 28) or control group (n = 23). Participators in PASET group received polyglycolic acid sutures alternatively embedded in abdominal I group and II group acupoints in odd and even number therapeutic courses, and participators in control group were required to perform lifestyle modification. The duration of the study was 10 weeks. Results It suggested that PASET significantly reduced weight, body mass index, hip circumference, waist circumference, waist/hip ratio, waist-to-height ratio and thickness of abdominal subcutaneous fat tissue compared with those before treatment (p < 0.01), but lifestyle modification only illustrated downward trend of weight (p < 0.05). Moreover, PASET group also improved the evaluated scores in aspects of physical function, self-esteem, public distress and sexual life, as well as decreased blood pressure, glycemia, low density lipoprotein, uric acid and the levels of tumor necrosis factor-alpha, interleukin-1β, and increased high density lipoprotein in comparison with those before treatment (p < 0.05), whose efficacies are superior to control group. Additionally, our results also indicate PASET is relative safe and its pain and discomfort can be tolerable. Conclusions PASET distinctly ameliorates anthropometric data and quality of life in obese population, which associates with improvements of metabolic profile and inflammatory response. Based on the advantageous actions, we think PASET is an effective therapeutic approach to simple obesity treatment. Trial registration ChiCTR, ChiCTR1800015591. Registered 10 April 2018, http://www.chictr.org.cn/showproj.aspx?proj=23258
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Affiliation(s)
- Li-Shu Chen
- 1Ningbo College of Health Sciences, Ningbo, 315100 China
| | - Yue-Ying Li
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060 China
| | - Hao Chen
- 3Nanjing University of Chinese Medicine, Nanjing, 210046 China
| | - Bo-Wen Liu
- 4Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210008 China
| | - Da-Wei Wang
- Shunde Hospital of Guangzhou University of Chinese Medicine, Shunde, 528333 China
| | - Yong-Hua Zhao
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, 999078 Macao SAR China
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Robinson J, Swift-Scanlan T, Salyer J. Obesity and 1-Year Mortality in Adults After Sepsis: A Systematic Review. Biol Res Nurs 2019; 22:103-113. [PMID: 31533460 DOI: 10.1177/1099800419876070] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
PURPOSE In recent years, researchers have noted an "obesity paradox," where individuals with obesity survive sepsis at higher rates than their nonobese counterparts. This systematic review summarizes the literature on studies examining the association between obesity and 1-year mortality among patients admitted with sepsis, severe sepsis, or septic shock. MATERIALS AND METHODS Using a comprehensive search strategy, a systematic review was conducted to identify studies examining the association of obesity and sepsis mortality. PubMed, Cumulative Index of Nursing and Allied Health Literature, and Elton B. Stephens Company host databases were searched for the terms sepsis, obesity, mortality, and adult. RESULTS The initial search identified 189 studies, 9 of which met inclusion criteria. Of these, four provided evidence that obese or very obese patients with sepsis have lower mortality than nonobese patients. Methodologic differences in the remaining five studies, which reported conflicting results, limit generalizability. CONCLUSION This systematic review on the association of obesity and sepsis mortality found three studies that demonstrated lower sepsis mortality among obese patients in the first 30 days and one showing that this protective effect extends up to 1 year. Given the increased number of patients surviving sepsis, it is important to consider long-term mortality and further describe the variables associated with increased survival.
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Affiliation(s)
- Jamie Robinson
- School of Nursing, Virginia Commonwealth University, Richmond, VA, USA
| | - Theresa Swift-Scanlan
- Biobehavioral Laboratory Services, School of Nursing, Virginia Commonwealth University, Richmond, VA, USA.,Department of Adult Health and Nursing Systems, School of Nursing, Virginia Commonwealth University, Richmond, VA, USA
| | - Jeanne Salyer
- Department of Adult Health and Nursing Systems, School of Nursing, Virginia Commonwealth University, Richmond, VA, USA
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Yang X, Wang J. The Role of Metabolic Syndrome in Endometrial Cancer: A Review. Front Oncol 2019; 9:744. [PMID: 31440472 PMCID: PMC6694738 DOI: 10.3389/fonc.2019.00744] [Citation(s) in RCA: 90] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Accepted: 07/24/2019] [Indexed: 12/12/2022] Open
Abstract
Endometrial cancer is one of the most common cancers of the female reproductive system. Although surgery, radiotherapy, chemotherapy, and hormone therapy can significantly improve the survival of patients, the treatment of patients with very early lesions and a strong desire to retain reproductive function or late recurrence is still in the early stages. Metabolic syndrome (MS) is a clustering of at least three of the five following medical conditions: central obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL). Obesity, diabetes and hypertension often coexist in patients with endometrial cancer, which increases the risk of endometrial cancer, also known as the "triple syndrome of endometrial cancer." In recent years, epidemiological and clinical studies have found that MS associated with metabolic diseases is closely related to the incidence of endometrial cancer. However, the key molecular mechanisms underlying the induction of endometrial cancer by MS have not been elucidated to date. Characterizing the tumor metabolism microenvironment will be advantageous for achieving a comprehensive view of the molecular mechanism of metabolic syndrome associated with endometrial cancer and for providing a new target for the treatment of endometrial cancer. This review focuses on recent advances in determining the role of metabolic syndrome-related factors and mechanisms in the pathogenesis of endometrial cancer. We suggest that interfering with the tumor metabolic microenvironment-related molecular signals may inhibit the occurrence of endometrial cancer.
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Affiliation(s)
- Xiao Yang
- Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing, China
| | - Jianliu Wang
- Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing, China
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Abstract
Immune cells infiltrate adipose tissues and provide a framework to regulate energy homeostasis. However, the precise underlying mechanisms and signaling by which the immune system regulates energy homeostasis in metabolic tissues remain poorly understood. Here, we show that the AT-rich interactive domain 5A (Arid5a), a cytokine-induced nucleic acid binding protein, is important for the maintenance of adipose tissue homeostasis. Long-term deficiency of Arid5a in mice results in adult-onset severe obesity. In contrast, transgenic mice overexpressing Arid5a are highly resistant to high-fat diet-induced obesity. Inhibition of Arid5a facilitates the in vitro differentiation of 3T3-L1 cells and fibroblasts to adipocytes, whereas its induction substantially inhibits their differentiation. Molecular studies reveal that Arid5a represses the transcription of peroxisome proliferator activated receptor gamma 2 (Ppar-γ2) due to which, in the absence of Arid5a, Ppar-γ2 is persistently expressed in fibroblasts. This phenomenon is accompanied by enhanced fatty acid uptake in Arid5a-deficient cells, which shifts metabolic homeostasis toward prolipid metabolism. Furthermore, we show that Arid5a and Ppar-γ2 are dynamically counterregulated by each other, hence maintaining adipogenic homeostasis. Thus, we show that Arid5a is an important negative regulator of energy metabolism and can be a potential target for metabolic disorders.
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Lacerda DR, Costa KA, Silveira ALM, Rodrigues DF, Silva AN, Sabino JL, Pinho V, Menezes GB, Soares DD, Teixeira MM, Ferreira AVM. Role of adipose tissue inflammation in fat pad loss induced by fasting in lean and mildly obese mice. J Nutr Biochem 2019; 72:108208. [PMID: 31473506 DOI: 10.1016/j.jnutbio.2019.06.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Revised: 05/18/2019] [Accepted: 06/06/2019] [Indexed: 02/06/2023]
Abstract
Inflammation induced by obesity contributes to insulin resistance and atherosclerosis. Indeed, high levels of proinflammatory cytokines trigger chronic low-grade inflammation and promote detrimental metabolic effects in the adipose tissue. On the other hand, inflammation seems to control fat pad expansion and to have important functions on lipolysis and glucose metabolism. Thus, it is possible that inflammation may also drive fat pad loss, as seen during long-fast periods. Herein, we have used fasting as a strategy to induce weight loss and evaluate the possible role of inflammation on adipose tissue remodeling. Male BALB-c mice were fed with chow diet (lean mice) or with high-carbohydrate refined diet (mildly obese mice) for 8 weeks. After that, animals were subjected to 24 h of fasting. There was a 63% reduction of adiposity in lean mice following fasting. Furthermore, the adipose tissue was enriched of immune cells and had a higher content of IL-6, TNF-alpha, IL-10, TGF-β and CXCL-1. Interestingly, mildly obese mice, subjected to the same 24-h fasting period, lost only 33% of their adiposity. Following fasting, these mice did not show any increment in leukocyte recruitment and cytokine levels, as did lean mice. Our findings indicate that inflammation participates in fat mass loss induced by fasting. Although the chronic low-grade inflammation seen in obesity is associated with metabolic diseases, a lower inflammatory response triggered by fasting in mildly obese mice impairs fat pad mobilization.
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Affiliation(s)
- Débora Romualdo Lacerda
- Department of Nutrition, Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
| | - Kátia Anunciação Costa
- Department of Nutrition, Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
| | - Ana Letícia Malheiros Silveira
- Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
| | - Débora Fernandes Rodrigues
- Department of Nutrition, Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
| | - Albena Nunes Silva
- Sport Center, Universidade Federal de Ouro Preto (CEDUFOP), Ouro Preto Minas Gerais, Brazil.
| | - Josiana Lopes Sabino
- Department of Nutrition, Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
| | - Vanessa Pinho
- Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
| | - Gustavo Batista Menezes
- Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
| | - Danusa Dias Soares
- Department of Physical Education School of Physical Education, Physiotherapy and Occupational Therapy, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
| | - Mauro Martins Teixeira
- Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
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Silva KR, Baptista LS. Adipose-derived stromal/stem cells from different adipose depots in obesity development. World J Stem Cells 2019; 11:147-166. [PMID: 30949294 PMCID: PMC6441940 DOI: 10.4252/wjsc.v11.i3.147] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2018] [Revised: 01/27/2019] [Accepted: 02/28/2019] [Indexed: 02/06/2023] Open
Abstract
The increasing prevalence of obesity is alarming because it is a risk factor for cardiovascular and metabolic diseases (such as type 2 diabetes). The occurrence of these comorbidities in obese patients can arise from white adipose tissue (WAT) dysfunctions, which affect metabolism, insulin sensitivity and promote local and systemic inflammation. In mammals, WAT depots at different anatomical locations (subcutaneous, preperitoneal and visceral) are highly heterogeneous in their morpho-phenotypic profiles and contribute differently to homeostasis and obesity development, depending on their ability to trigger and modulate WAT inflammation. This heterogeneity is likely due to the differential behavior of cells from each depot. Numerous studies suggest that adipose-derived stem/stromal cells (ASC; referred to as adipose progenitor cells, in vivo) with depot-specific gene expression profiles and adipogenic and immunomodulatory potentials are keys for the establishment of the morpho-functional heterogeneity between WAT depots, as well as for the development of depot-specific responses to metabolic challenges. In this review, we discuss depot-specific ASC properties and how they can contribute to the pathophysiology of obesity and metabolic disorders, to provide guidance for researchers and clinicians in the development of ASC-based therapeutic approaches.
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Affiliation(s)
- Karina Ribeiro Silva
- Laboratory of Tissue Bioengineering, Directory of Metrology Applied to Life Sciences, National Institute of Metrology, Quality and Technology, Duque de Caxias, RJ 25250-020, Brazil
- Post-Graduation Program of Biotechnology, National Institute of Metrology, Quality and Technology, Duque de Caxias, RJ 25250-020, Brazil
| | - Leandra Santos Baptista
- Laboratory of Tissue Bioengineering, Directory of Metrology Applied to Life Sciences, National Institute of Metrology, Quality and Technology, Duque de Caxias, RJ 25250-020, Brazil
- Post-Graduation Program of Biotechnology, National Institute of Metrology, Quality and Technology, Duque de Caxias, RJ 25250-020, Brazil
- Multidisciplinary Center for Biological Research (Numpex-Bio), Federal University of Rio de Janeiro Campus Duque de Caxias, Duque de Caxias, RJ 25245-390, Brazil
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