Succinate Enhances Lipolysis and Decreases Adipocytes Size in Both Subcutaneous and Visceral Adipose Tissue from High-Fat-Diet-Fed Obese Mice
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ABSTRACT:
SUBMITTER: Ji T
PROVIDER: S-EPMC10706267 | biostudies-literature | 2023 Nov
REPOSITORIES: biostudies-literature
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Project description:Adipose tissue plays a key role in the development of type-2 diabetes via the secretion of adipokines. The current study investigated if secretion media derived from intact visceral (VAT) and subcutaneous (SAT) adipose tissues from extremely obese men and women differently suppressed insulin signaling in human skeletal myotubes derived from a healthy, non-diabetic male and female donor, respectively. Adipose tissue samples were collected from men and women during laparoscopic bariatric surgery. In general, secretion media collected from both SAT and VAT depots caused impaired insulin signaling in myotubes, independent of sex. In females, this was true regardless of the protein kinase B (Akt) phosphorylation site (Akt Thr308 and Akt Ser473) assessed (p < 0.01). In males, both SAT and VAT secretion media reduced Akt Thr308 activation in insulin-stimulated myotubes compared to controls (p < 0.001); however, only the VAT secretion media impaired Akt Ser473 phosphorylation. Independent of sex, 13 out of 18 detected cytokines, chemokines, and growth factors were more abundant in VAT versus SAT secretion media (p < 0.01). Both SAT and VAT secretion media from obese men and women acutely suppress insulin signaling in myotubes, despite different secretion profiles. We propose that this crosstalk model will help to extend our understanding of the interplay between adipose and muscle, as well as the pathogenesis of type-2 diabetes.
| S-EPMC5454872 | biostudies-literature
Project description:UnlabelledA number of clinical and biochemical studies demonstrate that obesity and insulin resistance are associated with increases in oxidative stress and inflammation. Paradoxically, insulin sensitivity can be enhanced by oxidative inactivation of cysteine residues of phosphatases, and inflammation can be reduced by S-glutathionylation with formation of protein-glutathione mixed disulfides (PSSG). Although oxidation of protein-bound thiols (PSH) is increased in multiple diseases, it is not known whether there are changes in PSH oxidation species in obesity.ObjectiveIn this work, the hypothesis that obesity is associated with decreased levels of proteins containing oxidized protein thiols was tested.Design and methodsThe tissue levels of protein sulfenic acids (PSOH) and PSSG in liver, visceral adipose tissue, and skeletal muscle derived from glucose intolerant, obese-prone Sprague-Dawley rats were examined.ResultsThe data in this study indicate that decreases in PSSG content occurred in liver (44%) and adipose (26%) but not skeletal muscle in obese rats that were fed a 45% fat-calorie diet versus lean rats that were fed a 10% fat-calorie diet. PSOH content did not change in the tissue between the two groups. The activity of the enzyme glutaredoxin (GLRX) responsible for reversal of PSSG formation did not change in muscle and liver between the two groups. However, levels of GLRX1 were elevated 70% in the adipose tissue of the obese, 45% fat calorie-fed rats.ConclusionThese are the first data to link changes in S-glutathionylation and GLRX1 to adipose tissue in the obese and demonstrate that redox changes in thiol status occur in adipose tissue as a result of obesity.
| S-EPMC3610808 | biostudies-literature
Project description:Obesity is associated with a disturbed adipose tissue (AT) function characterized by adipocyte hypertrophy, an impaired lipolysis and pro-inflammatory phenotype, which contributes to insulin resistance (IR). We investigated whether AT phenotype in different AT depots of obese individuals with and without type 2 diabetes mellitus (T2DM) is associated with whole-body IR. Subcutaneous (SC) and visceral (V) AT biopsies from 18 lean, 17 obese and 8 obese T2DM men were collected. AT phenotype was characterized by ex vivo measurement of basal and stimulated lipolysis (mature adipocytes), adipocyte size distribution (AT tissue sections) and AT immune cells (flow cytometry). In VAT, mean adipocyte size, CD45+ leukocytes and M1 macrophages were significantly increased in both obese groups compared to lean individuals. In SCAT, despite adipocyte hypertrophy, no significant differences in immune cell populations between groups were found. In SCAT, multiple linear regression analysis showed that none of the AT phenotype markers independently contributed to HOMA-IR while in VAT, mean adipocyte size was significantly related to HOMA-IR. In conclusion, beside adipocyte hypertrophy in VAT, M1 macrophage- or B-cell-mediated inflammation, may contribute to IR, while inflammation in hypertrophic SCAT does not seem to play a major role in IR.
| S-EPMC5856747 | biostudies-literature
Project description:ContextAdipose tissue distribution is a key factor influencing metabolic health and risk in obesity-associated comorbidities.ObjectiveHere we aim to compare the proteomic profiles of mature adipocytes from different depots.MethodsAbdominal subcutaneous (SA) and omental visceral adipocytes (VA) were isolated from paired adipose tissue biopsies obtained during bariatric surgery on 19 severely obese women (body mass index > 30 kg/m2) and analyzed using state-of-the-art mass spectrometry. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed to investigate proteome signature properties and to examine a possible association of the protein expression with the clinical data.ResultsWe identified 3686 protein groups and found 1140 differentially expressed proteins (adj. P value < 0.05), of which 576 proteins were upregulated in SA and 564 in VA samples. We provide a global protein profile of abdominal SA and omental VA, present the most differentially expressed pathways and processes distinguishing SA from VA, and correlate them with clinical and body composition data. We show that SA are significantly more active in processes linked to vesicular transport and secretion, and to increased lipid metabolism activity. Conversely, the expression of proteins involved in the mitochondrial energy metabolism and translational or biosynthetic activity is higher in VA.ConclusionOur analysis represents a valuable resource of protein expression profiles in abdominal SA and omental VA, highlighting key differences in their role in obesity.
| S-EPMC8851937 | biostudies-literature
Project description:The metabolic syndrome (MetS) is a cluster of the most dangerous heart attack risk factors: diabetes or raised fasting plasma glucose, abdominal obesity, high cholesterol and high blood pressure. The goal of this study is to compare the state of the main features of obesity-associated white adipose tissue (WAT) dysfunction in 66 women with severe obesity without (MetS-) or with MetS (MetS+). Fat cell area, adipocyte size distribution and histological fibrosis were analysed in visceral (VAT) and abdominal subcutaneous WAT (SAT) in 33 age- and BMI-matched pairs of MetS- and MetS+ subjects. The mRNA expression of 93 genes implicated in obesity-associated WAT dysfunction was analysed by RT-qPCR in both fat depots. MetS+ females showed higher adipocyte hypertrophy in both fat depots and increased fibrosis and expression of macrophage and hypoxia markers in SAT. Transcriptional data suggest increased fatty acid oxidation in SAT and impaired thermogenesis and extracellular matrix remodelling in VAT from MetS+ subjects. A sPLS-DA model, including SAT expression of PPARA and LEPR genes identified MetS with an AUC = 0.87. Despite equal age, BMI and body composition, MetS+ females display morphological and transcriptional differences in both WAT depots, especially in SAT. These factors may contribute to the transition to MetS.
| S-EPMC8878297 | biostudies-literature
Project description:Distinct characteristics of adipose tissue at different localization of human body has shown greater significance in development of metabolic disorders. Visceral adipose tissue in particular is known to be associated with obesity related metabolic complications that include type II diabetes. In this experiment, we attempt to profile transcriptome signatures of adipocyte, stromal vascular fraction (SVF) and adipose tissue from subcutaneous and visceral adipose tissue from obese individuals.
2019-11-04 | GSE135776 | GEO
Project description:Adipose tissue (AT) distribution is an important determinant of cardiometabolic health. Increased visceral adiposity has been associated with a higher risk of obesity-related diseases. An important step in deciphering the molecular complexity of subcutaneous AT (SAT) and visceral AT (VAT) is to elucidate the molecular composition of the principal AT cell type, adipocytes. We present a comprehensive protein expression profile of abdominal subcutaneous (SA) and omental visceral adipocytes (VA). We isolated adipocytes from paired AT biopsies obtained during bariatric surgery of 19 morbidly obese women (BMI > 30 kg/m2) and performed state-of-the-art mass spectrometry to investigate their proteome profiles. We identified 3,686 proteins groups and found 1,140 differentially expressed proteins (adj. p-value < 0.05), of which 576 proteins were upregulated in SA and 564 in VA samples. In addition to providing a global protein profile of abdominal SA and omental VA, we also present the most differentially expressed pathways and processes distinguishing SA from VA. We show that SA are significantly more active in processes linked to vesicular transport and secretion, and also to increased lipid metabolism activity. Conversely, the expression of proteins involved in the mitochondrial energy metabolism and translational or biosynthetic activity is higher in VA. We also performed prediction analyses of differentially expressed putative secreted proteins, which revealed a significantly higher number of potentially secreted proteins in SA compared to VA. Our analysis represents a valuable resource of protein expression profiles in abdominal SA and omental VA, highlighting key differences in their role in obesity. Additionally, we predict possible protein targets among secreted proteins, which may be utilized for the further investigation of the role of different AT depots in obesity using peripheral blood.
2021-11-04 | PXD024734 | Pride
Project description:In the context of obesity, strong evidences support a distinctive pathological contribution of adipose tissue depending on its anatomical site of accumulation. Therefore, subcutaneous adipose tissue (SAT) has been lately considered metabolically benign compared to visceral fat (VAT), whose location is associated to the risk of developing cardiovascular disease, insulin resistance, and other associated comorbidities. Under the above situation, the chronic local inflammation that characterizes obese adipose tissue, has acquired a major role on the pathogenesis of obesity. In this work, we have analyzed for the first time human obese VAT and SAT secretomes using an improved quantitative proteomic approach for the study of tissue secretomes, Comparison of Isotope-Labeled Amino acid Incorporation Rates (CILAIR). The use of double isotope-labeling-CILAIR approach to analyze VAT and SAT secretomes allowed the identification of location-specific secreted proteins and its differential secretion. Additionally to the very high percentage of identified proteins previously implicated in obesity or in its comorbidities, this approach was revealed as a useful tool for the study of the obese adipose tissue microenvironment including extracellular matrix (ECM) remodeling and inflammatory status. The results herein presented reinforce the fact that VAT and SAT depots have distinct features and contribute differentially to metabolic disease.
| S-EPMC4648467 | biostudies-literature
Project description:OBJECTIVE:Visceral (VAT) and abdominal subcutaneous (SAT) adipose tissues contribute to obesity but may have different metabolic and atherosclerosis risk profiles. We sought to determine the associations of abdominal VAT and SAT mass with markers of cardiac and metabolic risk in a large, multiethnic, population-based cohort of obese adults. DESIGN AND METHODS:Among obese participants in the Dallas Heart Study, we examined the cross-sectional associations of abdominal VAT and SAT mass, assessed by magnetic resonance imaging (MRI) and indexed to body surface area (BSA), with circulating biomarkers of insulin resistance, dyslipidemia, and inflammation (n = 942); and with aortic plaque and liver fat by MRI and coronary calcium by computed tomography (n = 1200). Associations of VAT/BSA and SAT/BSA were examined after adjustment for age, sex, race, menopause, and body mass index. RESULTS:In multivariable models, VAT significantly associated with the homeostasis model assessment of insulin resistance (HOMA-IR), lower adiponectin, smaller LDL and HDL particle size, larger VLDL size, and increased LDL and VLDL particle number (p < 0.001 for each). VAT also associated with prevalent diabetes, metabolic syndrome, hepatic steatosis, and aortic plaque (p < 0.001 for each). VAT independently associated with C-reactive protein but not with any other inflammatory biomarkers tested. In contrast, SAT associated with leptin and inflammatory biomarkers, but not with dyslipidemia or atherosclerosis. Associations between SAT and HOMA-IR were significant in univariable analyses but attenuated after multivariable adjustment. CONCLUSION:VAT associated with an adverse metabolic, dyslipidemic, and atherogenic obesity phenotype. In contrast, SAT demonstrated a more benign phenotype, characterized by modest associations with inflammatory biomarkers and leptin, but no independent association with dyslipidemia, insulin resistance, or atherosclerosis in obese individuals. These findings suggest that abdominal fat distribution defines distinct obesity sub-phenotypes with heterogeneous metabolic and atherosclerosis risk.
| S-EPMC3751977 | biostudies-literature
Project description:Subcutaneous adipose tissue and visceral adipose tissue samples were obtained from severely obese individuals that underwent bariatric surgery. The goal of this study was to compare genome-wide gene expression levels in the two tissue types from healthy and unhealthy severely obese individuals. Whole-transcriptome subcutaneous adipose tissue gene expression levels were determined in 73 individuals with a BMI >35 kg/m2. Whole-transcriptome visceral adipose tissue gene expression levels were determined in 69 individuals with a BMI >35 kg/m2. Modules of co-expressed genes likely to be functionally related were identfied and correlated with BMI, plasma levels of glucose, insulin, HbA1c, triglycerides, non-esterified fatty acids, ALAT, ASAT, C-reactive protein, and LDL- and HDL cholesterol.
2010-06-03 | GSE22070 | GEO