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).

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.

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.

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.

Project description:Breed, gender and diet are factors affecting porcine metabolism. The aim of this study has been to investigate the gene expression patterns of the major sites for lipid metabolism, liver and fat, conditional on gender and on a moderate feeding restriction in Iberian pigs, as a model of obese porcine breed. Our results show that tissue effect account for more differentially expressed genes than gender or feeding restriction. The results obtained from the comparison between tissues support the studies showing adipose tissue is not only a fat-storage depot, we report a high number of upregulated genes in adipose tissue which represent relevant biological functions such as carbohydrate and energy metabolisms and endocrine function. Besides, key genes implicated in lipid metabolism are specifically overrepresented in liver or fat, particularly the differentially expressed genes related to fatty acid synthesis support previous studies showing that in pig, as in cattle or sheep, this process largely occurs in fat. We identified metabolic differences between genders such as oxidation capacity or response to toxins, reflected at gene expression level in liver but no in adipose tissue, contrarily to previous studies. Finally, our results seem to indicate that a moderate feeding restriction does not have large effects on liver or fat gene expression of obese pigs. Although the list of differentially expressed genes due to the effect of feeding restriction is limited, we could identify expression differences in genes related to antiageing mechanisms associated with feeding restriction as enhancement of immune response and anticoagulation and the balance between prosurvival and cell-death. Breed, gender and diet are factors affecting porcine metabolism. The aim of this study has been to investigate the gene expression patterns of the major sites for lipid metabolism, liver and fat, conditional on gender and on a moderate feeding restriction in Iberian pigs, as a model of obese porcine breed. Our results show that tissue effect account for more differentially expressed genes than gender or feeding restriction. The results obtained from the comparison between tissues support the studies showing adipose tissue is not only a fat-storage depot, we report a high number of upregulated genes in adipose tissue which represent relevant biological functions such as carbohydrate and energy metabolisms and endocrine function. Besides, key genes implicated in lipid metabolism are specifically overrepresented in liver or fat, particularly the differentially expressed genes related to fatty acid synthesis support previous studies showing that in pig, as in cattle or sheep, this process largely occurs in fat. We identified metabolic differences between genders such as oxidation capacity or response to toxins, reflected at gene expression level in liver but no in adipose tissue, contrarily to previous studies. Finally, our results seem to indicate that a moderate feeding restriction does not have large effects on liver or fat gene expression of obese pigs. Although the list of differentially expressed genes due to the effect of feeding restriction is limited, we could identify expression differences in genes related to antiageing mechanisms associated with feeding restriction as enhancement of immune response and anticoagulation and the balance between prosurvival and cell-death. 16 liver and subcutaneous backfat samples from eight animals at slaughter, 211 days old, four males and four females, four under high feeding level and four under 20% restriction

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