Trait related and differential DNA Methylation in obese and normal weight Brazilian women.
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE166611 | GEO | 2021/02/12
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: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:Trait related and differential DNA Methylation in obese and normal weight Brazilian women.
| PRJNA701423 | ENA
Project description:Maternal obesity in pregnancy is associated with increased birth-weight, obesity and premature mortality in adult offspring. The Effect of Metformin on Maternal and Fetal Outcomes in Pregnant Obese Women (EMPOWaR) trial was a randomised, double-blind, placebo-controlled trial carried out to determine whether exposure to Metformin would affect the offspring birth-weight centile. Obese women exposed to Metformin had increased insulin sensitivity at 36 weeks of pregnancy, but there were no differences in offspring birthweight. We obtained the placentas from these women to determine whether there were differences in expression of genes regulating fetal growth and metabolism. In a complementary study we investigated DNA methylation in the same samples.
2019-01-31 | E-MTAB-6418 | biostudies-arrayexpress
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:Maternal obesity in pregnancy is associated with increased birth-weight, obesity and premature mortality in adult offspring. The Effect of Metformin on Maternal and Fetal Outcomes in Pregnant Obese Women (EMPOWaR) trial was a randomised, double-blind, placebo-controlled trial carried out to determine whether exposure to Metformin would affect the offspring birth-weight centile. Obese women exposed to Metformin had increased insulin sensitivity at 36 weeks of pregnancy, but there were no differences in offspring birthweight. We obtained the placentas from these women to determine whether there were differences in DNA methylation of genes regulating fetal growth and metabolism. In a related study we investigated the gene expression in the same samples.
2018-11-01 | E-MTAB-6421 | biostudies-arrayexpress
Project description:The aim of this study is to design and validate a test, METAHEALTH-TEST, based on gene expression analysis in blood cells, to quickly and easily analyse metabolic health. This test will be used to analyse metabolic improvement in overweight/obese individuals and in metabolically obese normal-weight (MONW) individuals after undergoing a weight loss intervention and/or an intervention for improvement in eating habits and lifestyle. Obesity and its medical complications are a serious health problem today. Using peripheral blood mononuclear cells (PBMC) as an easily obtainable source of transcriptomic biomarkers would allow to deepen into the knowledge of adaptations in response to increased adiposity that occur in internal homeostatic tissues, without the need of using invasive biopsies. Moreover, if PBMC were able to reflect lipid metabolism gene expression pattern recovery as a result of weight loss, it would provide valuable information to know the efficacy of therapies aimed at weight loss and, in any case, it would allow to personalize them according to the evolution of obese patients until the desired metabolic recovery is achieved.
2023-10-11 | GSE181339 | 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
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.
2015-09-15 | GSE67024 | GEO
Project description:Skeletal muscle (rectus femoris) gene expression was analyzed from diet-resistant and diet-sensitive obese women undergoing clinically supervised weight-loss at a weight management clinic The goal of the study was to characterize global gene expression profiles in skeletal muscle from obese women, prior to their participation in a clinically supervised, low-calorie diet, weight management program. Following entry into the weight-loss program, subjects can be categorized as being 'diet-sensitive' or 'diet-resistant' depending on the rates of weight loss achieved. In the current study, we selected an equal number of diet-sensitive and diet-resistant subjects for comparative expression profiling
2009-07-29 | GSE17371 | GEO