Project description:Objective: This work aimed at identifying and characterizing differences in subcutaneous adipose tissue (SAT) gene expression patterns between subjects succeeding weight control against subjects regaining weight 6 months after a low calorie diet program. Methods: Weight-reduced obese subjects from 8 European countries were randomized into 4 diets differing in protein and glycemic index. In addition to the anthropometric and plasma parameters, SAT biopsies were taken at the beginning (CID2) and the end (CID3) of the weight maintenance intervention. Pan-genomic cDNA microarrays were used to define SAT gene expression profiles at both CID2 and CID3 of 22 subjects succeeding weight maintenance (successful subjects; mean weight change= -2.6 ± 1.2 kg) and 22 subjects regaining weight (unsuccessful subjects; mean weight change= 3.9 ± 1.3 kg) among the 4 dietary arms. Results: Differences in SAT gene expression patterns between successful and unsuccessful groups were mainly due to weight variations rather to differences in diet macronutrient composition. An ANCOVA analysis with total energy intake at CID3 as covariant led us to the definition of 1339 differential genes. Functional analysis of differential genes showed that cellular growth and proliferation, inflammation, cell death, cancer, cellular function and maintenance were the main biological processes involving these differential genes. Overall design: SAT transcriptome was defined at the beginning (CID2) and at the end (CID3) of the dietary intervention program using a common reference design: Cyanine-5 dye was incorporated into all SAT samples, while a reference RNA pool made of the mix of commercial human liver, adipose tissue, and skeletal muscle RNA was labeled with cyanine-3 dye. Samples were hybridized to Agilent 44K whole human genome microarrays. Evolution in gene expression patterns after dietary intervention was tested in terms of the ratio after/before dietary intervention (CID3/CID2) ratio.
Project description:Objective: This work aimed at identifying and characterizing differences in subcutaneous adipose tissue (SAT) gene expression patterns between subjects succeeding weight control against subjects regaining weight 6 months after a low calorie diet program. Methods: Weight-reduced obese subjects from 8 European countries were randomized into 4 diets differing in protein and glycemic index. In addition to the anthropometric and plasma parameters, SAT biopsies were taken at the beginning (CID2) and the end (CID3) of the weight maintenance intervention. Pan-genomic cDNA microarrays were used to define SAT gene expression profiles at both CID2 and CID3 of 22 subjects succeeding weight maintenance (successful subjects; mean weight change= -2.6 ± 1.2 kg) and 22 subjects regaining weight (unsuccessful subjects; mean weight change= 3.9 ± 1.3 kg) among the 4 dietary arms. Results: Differences in SAT gene expression patterns between successful and unsuccessful groups were mainly due to weight variations rather to differences in diet macronutrient composition. An ANCOVA analysis with total energy intake at CID3 as covariant led us to the definition of 1339 differential genes. Functional analysis of differential genes showed that cellular growth and proliferation, inflammation, cell death, cancer, cellular function and maintenance were the main biological processes involving these differential genes.
Project description:Severe obesity (SO) affects about 6% of youth in US, augmenting the risks for cardiovascular disease and Type 2 diabetes. Herein, we obtained paired omental (omVAT) and abdominal subcutaneous (SAT) adipose tissue biopsies from obese girls with SO, undergoing sleeve gastrectomy (SG), to test whether differences in cellular and transcriptomic profiles between omVAT and SAT depots affect insulin sensitivity differentially. Following weight loss, these analyses were repeated in a subgroup of subjects having a second SAT biopsy. We found that omVAT displayed smaller adipocytes compared to SAT, increased lipolysis through adipose triglyceride lipase (ATGL) phosphorylation, reduced inflammation and increased expression of browning/beige markers. Contrary to omVAT, SAT adipocyte diameter correlated with insulin resistance. Following SG, both weight and insulin sensitivity improved markedly in all subjects. SAT adipocytes size became smaller showing an increased lipolysis through perilipin-1 phosphorylation, decreased inflammation and increased expression in browning/beige markers. In summary, in adolescent girls with SO, both omVAT and SAT depots showed distinct cellular and transcriptomic profiles. Following weight loss, the SAT depot changed its cellular morphology and transcriptomic profiles into a more favorable one. These changes in the SAT depot may play a fundamental role in the resolution of insulin resistance.
Project description:Using RNA isolated from subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) samples obtained from control and class I, II and III obese patients undergoing inguinal hernia repair and laparoscopic cholecystectomy, we compared the gene expression profiles between SAT and VAT using microarrays and validated the findings by real-time quantitative PCR.
Project description:Using RNA isolated from subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) samples obtained from control and class I, II and III obese patients undergoing inguinal hernia repair and laparoscopic cholecystectomy, we compared the gene expression profiles between SAT and VAT using microarrays and validated the findings by real-time quantitative PCR. Two-condition experiment, SAT vs. VAT tissue. Biological replicates: 8 SAT replicates, 8 VAT replicates.
Project description:In addition to total body fat, the regional distribution and inflammatory status of enlarged adipose tissue are strongly linked to metabolic and cardiovascular complications of obesity. We recently showed that the severity of liver non-alcoholic histopathology in obese subjects increased with the amounts of macrophages in visceral adipose tissue (VAT), while no relation was found with the subcutaneous adipose tissue (SAT). In the abdominal region, SAT is anatomically divided into superficial (sSAT) and deep (dSAT) layers. The aim of the present study was to test the hypothesis that these distinct compartments differentially contribute to hepatic alteration in obesity. Total RNA was isolated from two different strata of human adipose tissue of 8 subjects.
Project description:Context: It is not known whether biological differences reported between subcutaneous (SAT) and visceral (VAT) adipose tissue depots underlie the pathogenicity of visceral fat. Objective: We compared SAT and VAT gene expression according to obesity, visceral fat accumulation, insulin resistance and presence of the metabolic syndrome. Design: Subjects were assigned into 4 groups (lean, overweight, obese and obese with metabolic syndrome). Setting: Subjects were recruited at a university hospital. Patients: 32 women were included. Main Outcome Measures: Anthropometric measurements, euglycemic hyperinsulinemic clamps, blood analyses and computed tomography scans were performed and paired samples of SAT and VAT were obtained for DNA microarray-based gene expression profiling.
Project description:To evaluate wether miRNA expression patterns contributes to obesity total RNA were purified from subcutaneous adipose tissue (SAT)and used in miRNA microarrays. Platform contain LNA-modified probes for all human miRNAs present in release 8.2 of the miRBase microRNA Registry. Two RNA pools from 3 non obese men (CM) and from 5 non obese women (CW) were used as controls. Expression profiling revealed that a large set of miRNAs is expressed in SAT. Forty two miRNAs changed by at least 1.5 folds in 17/20 obese subjects versus non obese control pool. Particularly, 21/42 were up-regulated and 21/42 were down-regulated. Among the differentially expressed miRNA, miR-519d, miR-498 and miR-150 were up-regulated, miR-659 and miR-371-3p_MM2 were down-regulated consistently in 20/20 obese subjects.
Project description:In addition to total body fat, the regional distribution and inflammatory status of enlarged adipose tissue are strongly linked to metabolic and cardiovascular complications of obesity. We recently showed that the severity of liver non-alcoholic histopathology in obese subjects increased with the amounts of macrophages in visceral adipose tissue (VAT), while no relation was found with the subcutaneous adipose tissue (SAT). In the abdominal region, SAT is anatomically divided into superficial (sSAT) and deep (dSAT) layers. The aim of the present study was to test the hypothesis that these distinct compartments differentially contribute to hepatic alteration in obesity.
Project description:Efficient collagen degradation is essential for adaptive subcutaneous adipose tissue (SAT) expansion that protects against ectopic lipid deposition during weight gain. Here, we aimed to further define the mechanism for this collagenolytic process. We show that loss of collagen type-1 (CT1) and increased CT1-fragment levels in expanding SAT are associated with proliferation of resident M2-like macrophages that display increased CD206-mediated engagement in collagen endocytosis compared to chow-fed controls. Blockage of CD206 during acute diet-induced weight gain leads to SAT CT1-fragment accumulation associated with elevated inflammation and fibrosis markers. Moreover, the collagen endocytosis engagement of SAT macrophages is dramatically reduced in obesity along with elevated levels of short collagen fragments. Finally, we show that such fragments provoke M2-macrophage proliferation and fibroinflammatory changes in vitro. Thus, our data delineate the importance of a macrophage-collagen axis in physiological SAT expansion. Further understanding of this process can define novel targets in obesity-related disorders.