Skeletal muscle tissue RNA-Seq and RRBS in T2D, Obese and Active subjects
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE196387 | GEO | 2023/08/11
REPOSITORIES: GEO
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Project description:Background/Objectives: Obese subjects have increased number of enlarged fat cells which are reduced in size but not number in post-obesity. We performed DNA methylation profiling in fat cells with the aim of identifying differentially methylated DNA sites (DMS) linked to adipose hyperplasia (many small fat cells) in post-obesity. Subjects/Methods: Genome-wide DNA methylation was analyzed in abdominal subcutaneous fat cells from 16 women examined two years after gastric bypass surgery at a post-obese state (BMI 26±2 kg/m2, mean±s.d.) and 14 never-obese women (BMI 25±2 kg/m2). Gene expression was analyzed in subcutaneous adipose tissue from 9 women in each group. In a secondary analysis, we examined DNA methylation and expression of adipogenesis genes in 15 and 11 obese women, respectively. Results: The average degree of DNA methylation of all analyzed CpG-sites was lower in fat cells from post-obese as compared to never-obese women (P=0.014). 8,504 CpG sites were differentially methylated in fat cells from post-obese versus never-obese women (false discovery rate 1%). DMS were under-represented in CpG-islands and surrounding shores. The 8,504 DMS mapped to 3,717 unique genes; these genes were over-represented in cell differentiation pathways. Notably, 27% of genes linked to adipogenesis (i.e. 35 of 130) displayed DMS (adjusted P=10−8) in post-obese versus never-obese women. Next, we explored DNA methylation and expression of genes linked to adipogenesis in more detail in adipose tissue samples. DMS annotated to adipogenesis genes were not accompanied by differential gene expression in post-obese compared to never-obese women. In contrast, adipogenesis genes displayed differential DNA methylation accompanied by altered expression in obese women, Conclusions: Global CpG hypomethylation and overrepresentation of DMS in adipogenesis genes in fat cells may contribute to adipose hyperplasia in post-obese women. Post obese=16, Control group=14.
2015-05-06 | E-GEOD-58622 | biostudies-arrayexpress
Project description:Our previous observation found CD27 negative MAIT cell subset is associated with T2D progression in overweight/obese patients. To identify the difference of functional properties between CD27 negative and positive MAIT subsets under obesity related T2D condition, we isolated circulating CD27+ or CD27- CD3+ CD161+ TCR Va7.2+ MAIT cells from PBMC of three diabetic obese patients and performed bulk RNA-seq based on Smart-seq2 protocol. By the comparison of CD27- and CD27+ MAIT cells, we found CD27- MAIT cell exhibit an increased mitochondrial mass and decreased response to bacterium transcriptional pattern compared to CD27+ MAIT cells in diabetic obese patients, indicating the imbalanced cell-bacteria interaction might contribute to T2D progression in overiweight/obese people.
2022-05-24 | GSE187349 | GEO
Project description:Background/Objectives: Obese subjects have increased number of enlarged fat cells which are reduced in size but not number in post-obesity. We performed DNA methylation profiling in fat cells with the aim of identifying differentially methylated DNA sites (DMS) linked to adipose hyperplasia (many small fat cells) in post-obesity. Subjects/Methods: Genome-wide DNA methylation was analyzed in abdominal subcutaneous fat cells from 16 women examined two years after gastric bypass surgery at a post-obese state (BMI 26±2 kg/m2, mean±s.d.) and 14 never-obese women (BMI 25±2 kg/m2). Gene expression was analyzed in subcutaneous adipose tissue from 9 women in each group. In a secondary analysis, we examined DNA methylation and expression of adipogenesis genes in 15 and 11 obese women, respectively. Results: The average degree of DNA methylation of all analyzed CpG-sites was lower in fat cells from post-obese as compared to never-obese women (P=0.014). 8,504 CpG sites were differentially methylated in fat cells from post-obese versus never-obese women (false discovery rate 1%). DMS were under-represented in CpG-islands and surrounding shores. The 8,504 DMS mapped to 3,717 unique genes; these genes were over-represented in cell differentiation pathways. Notably, 27% of genes linked to adipogenesis (i.e. 35 of 130) displayed DMS (adjusted P=10−8) in post-obese versus never-obese women. Next, we explored DNA methylation and expression of genes linked to adipogenesis in more detail in adipose tissue samples. DMS annotated to adipogenesis genes were not accompanied by differential gene expression in post-obese compared to never-obese women. In contrast, adipogenesis genes displayed differential DNA methylation accompanied by altered expression in obese women, Conclusions: Global CpG hypomethylation and overrepresentation of DMS in adipogenesis genes in fat cells may contribute to adipose hyperplasia in post-obese women.
2015-05-06 | GSE58622 | GEO
Project description:White adipose tissue (WAT) plays a critical role in whole-body energy homeostasis. In this study, we established the differential proteomic signatures of WAT in glucose-tolerant lean and obese individuals and patients with type 2 diabetes (T2D) and in response to 8 weeks of high intensity interval training (HIIT). We combined a high-throughput and reproducible mass spectrometry-based proteomics pipeline and identified a total of 3773 proteins. We find that a majority of regulated proteins displayed progression from lean to obese and T2D individuals and were highly associated with clinical measures of glucose homeostasis (e.g., insulin sensitivity, HbA1c) and they could, therefore, serve as potential disease biomarkers. Interestingly, HIIT induced a strong increase in WAT ferritin levels independent of group. WAT ferritin levels strongly correlated with individual insulin sensitivity. Thus, we report novel proteomic signatures of WAT related to obesity and T2D and highlight an unrecognized role of human WAT iron metabolism in exercise training adaptations.
2024-01-10 | PXD040434 | Pride
Project description:Background Obesity is associated with changes in fat cell gene expression and metabolism. What drives these changes is not well understood. We aimed to explore fat cell epigenetics, i.e., DNA methylation, as one mediator of gene regulation, in obese women. The global DNA methylome for abdominal subcutaneous fat cells was compared between 15 obese case (BMI 41.4 ± 4.4 kg/m 2 , mean ± SD) and 14 never-obese control women (BMI 25.2 ± 2.5 kg/m 2 ). Global array-based transcriptome analysis was analyzed for subcutaneous white adipose tissue (WAT) from 11 obese and 9 never-obese women. Limma was used for statistical analysis. Results We identified 5529 differentially methylated DNA sites (DMS) for 2223 differentially expressed genes between obese cases and never-obese controls (false discovery rate <5 %). The 5529 DMS displayed a median difference in beta value of 0.09 (range 0.01 to 0.40) between groups. DMS were under-represented in CpG islands and in promoter regions, and over-represented in open sea-regions and gene bodies. The 2223 differentially expressed genes with DMS were over-represented in key fat cell pathways: 31 of 130 (25 %) genes linked to “adipogenesis” (adjusted P = 1.66 × 10 −11 ), 31 of 163 (19 %) genes linked to “insulin signaling” (adjusted P = 1.91 × 10 −9 ), and 18 of 67 (27 %) of genes linked to “lipolysis” (P = 6.1 × 10 −5 ). In most cases, gene expression and DMS displayed reciprocal changes in obese women. Furthermore, among 99 candidate genes in genetic loci associated with body fat distribution in genome-wide association studies (GWAS); 22 genes displayed differential expression accompanied by DMS in obese versus never-obese women (P = 0.0002), supporting the notion that a significant proportion of gene loci linked to fat distribution are epigenetically regulated. Conclusions Subcutaneous WAT from obese women is characterized by congruent changes in DNA methylation and expression of genes linked to generation, distribution, and metabolic function of fat cells. These alterations may contribute to obesity-associated metabolic disturbances such as insulin resistance in women. The global DNA methylome in abdominal subcutaneous fat cells was compared between 15 obese cases (BMI 41.4±4.4 kg/m2, mean ± SD) and 14 never-obese control women (BMI 25.2±2.5 kg/m2).
2015-09-15 | E-GEOD-67024 | biostudies-arrayexpress
Project description:Type 2 diabetes (T2D) is associated with cardiovascular-renal complications and premature death. Although most patients with T2D are obese, not all obese individuals develop T2D. Thus, an understanding of the mechanistic relationships between obesity and T2D is crucial. In this study, using subcutaneous (SAT) and visceral adipose tissues (VAT) from obese individuals with or without T2D collected during metabolic surgery, integration of the transcriptomes and methylomes of VAT and SAT with publicly available tissue-specific regulatory networks, we discovered the close relation between T2D and inflammatory response in both SAT and VAT in obese individuals, although less differences were observed respectively in transcriptome or methylome. Specifically, a HOX gene family-enriched functional epigenetic sub-network in T2D-SAT, as well as a novel such sub-network was discovered, which involved multiple genes implicated in activation of obesity-induced inflammatory response. Our integrated approach of using biosamples, multi-omic data and public databases to understand complex diseases for discovery of novel biology, including biomarkers and drug targets, can be applied to diseases other than T2D and obesity.
2021-12-20 | GSE162166 | GEO
Project description:Resveratrol is a naturally occurring compound that profoundly affects energy metabolism and mitochondrial function and serves as a calorie restriction mimetic, at least in animal models of obesity. Here we treated 10 healthy, obese men with placebo and 150 mg/day resveratrol in a randomized double-blind cross-over study for 30 days. Resveratrol supplementation significantly reduced sleeping- and resting metabolic rate. In muscle, resveratrol activated AMPK, increased SIRT1 and PGC-1alpha protein levels, increased citrate synthase activity, and improved muscle mitochondrial respiration on a fatty acid-derived substrate. Furthermore, resveratrol elevated intramyocellular lipid levels, and decreased intrahepatic lipid content, circulating glucose, triglycerides, alanine-aminotransferase, and inflammation markers. Systolic blood pressure dropped and HOMA index improved after resveratrol. In the postprandial state, adipose tissue lipolysis and plasma fatty acid and glycerol decreased. In conclusion, we demonstrate that 30 days of resveratrol supplementation induces profound metabolic changes in obese subjects, mimicking the effects of calorie restriction. double-blind randomized cross-over study, Expression profiling by microarray
2011-11-08 | E-GEOD-32357 | biostudies-arrayexpress
Project description:Our main purpose is to screen specific biomarkers for supporting diagnoses of type-2 diabetic nephropathy (T2DN), type-2 diabetic retinopathy (T2DR), and type-2 diabetes mellitus (T2D) without these complications. The RNA expression database was built to study T2D in humans with the performance of the Clariom™ D Assay, human. The notable highlight of the analysis results shows there are three main groups which include one control group and two diabetic groups. Interestingly, the diabetic groups share some aging-related pathways, especially fatty acid metabolism. On the other hand, B group with higher BMI coverage has many abundant coding genes in fatty acid degradation, while C group with lower BMI coverage involves in fatty acid elongation. It can be classified into obese and non-obese groups proportionally. In addition, the obese group consists of two T2DN-related cases without an independent T2DR_related case, which is contrary to the non-obese group has all three cases. It means that T2DR can be rarely found in overweight T2D-patients.
2023-07-07 | GSE189005 | GEO
Project description:Obesity and type 2 diabetes (T2D) remain major global healthcare challenges and developing therapeutics necessitate using nonhuman primate models. Here, we present transcriptomic and proteomic analyses of all the major organs of cynomolgus monkeys with spontaneous obesity or T2D in comparison to healthy controls. Molecular changes occur predominantly in the adipose tissues of obesity individuals, while extensive expression perturbations of T2D individuals are observed in many tissues, such as liver, kidney, brain, and heart. Immune response-related pathways are upregulated in obesity and T2D, whereas metabolism and mitochondrial pathways are downregulated. Incorporating human single-cell RNA sequencing findings corroborates the role of macrophages and monocytes in obesity. Moreover, we highlight some potential therapeutic targets including SLC2A1 and PCSK1 in obesity as well as SLC30A8 and SLC2A2 in T2D. Our findings provide insights into the tissue-specific molecular foundations of obesity and T2D and reveal the mechanistic links between these two metabolic disorders.
2023-06-22 | GSE188418 | GEO
Project description:BACKGROUND: Obesity is associated with changes in fat cell gene expression and metabolism. What drives these changes is not well understood. We aimed to explore fat cell epigenetics, i.e., DNA methylation, as one mediator of gene regulation, in obese women. The global DNA methylome for abdominal subcutaneous fat cells was compared between 15 obese case (BMI 41.4?±?4.4 kg/m(2), mean?±?SD) and 14 never-obese control women (BMI 25.2?±?2.5 kg/m(2)). Global array-based transcriptome analysis was analyzed for subcutaneous white adipose tissue (WAT) from 11 obese and 9 never-obese women. Limma was used for statistical analysis. RESULTS: We identified 5529 differentially methylated DNA sites (DMS) for 2223 differentially expressed genes between obese cases and never-obese controls (false discovery rate <5 %). The 5529 DMS displayed a median difference in beta value of 0.09 (range 0.01 to 0.40) between groups. DMS were under-represented in CpG islands and in promoter regions, and over-represented in open sea-regions and gene bodies. The 2223 differentially expressed genes with DMS were over-represented in key fat cell pathways: 31 of 130 (25 %) genes linked to "adipogenesis" (adjusted P?=?1.66?×?10(-11)), 31 of 163 (19 %) genes linked to "insulin signaling" (adjusted P?=?1.91?×?10(-9)), and 18 of 67 (27 %) of genes linked to "lipolysis" (P?=?6.1?×?10(-5)). In most cases, gene expression and DMS displayed reciprocal changes in obese women. Furthermore, among 99 candidate genes in genetic loci associated with body fat distribution in genome-wide association studies (GWAS); 22 genes displayed differential expression accompanied by DMS in obese versus never-obese women (P?=?0.0002), supporting the notion that a significant proportion of gene loci linked to fat distribution are epigenetically regulated. CONCLUSIONS: Subcutaneous WAT from obese women is characterized by congruent changes in DNA methylation and expression of genes linked to generation, distribution, and metabolic function of fat cells. These alterations may contribute to obesity-associated metabolic disturbances such as insulin resistance in women.
2017-02-09 | GSE24884 | GEO