Abstract
BackgroundObesity 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/m2, mean ± SD) and 14 never-obese control women (BMI 25.2 ± 2.5 kg/m2). 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.ResultsWe 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.ConclusionsSubcutaneous 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-015-0126-9) contains supplementary material, which is available to authorized users.
Highlights
Obesity is associated with changes in fat cell gene expression and metabolism
We report that several genes in pathways involved in adipogenesis, insulin signaling, and lipolysis display DNA methylated sites (DMS) accompanied by differential gene expression in obese women
The 5529 DMS displayed a median difference in beta value of 0.09 between the obese cases and never-obese controls
Summary
Obesity is associated with changes in fat cell gene expression and metabolism. What drives these changes is not well understood. Through large genome-wide association studies (GWAs), a number of susceptibility genes for obesity and related metabolic disturbances have been mapped, but together they explain no more than a minor proportion of the heritability/variation in these phenotypes, and the culprit genes are in most cases unknown [7,8,9,10]. Epigenetic modifications, such as DNA methylation and histone modifications, constitute an additional layer regulating gene expression and effecting phenotypes and the development of various states of disease [11]. The reported absolute differences in DNA methylation at specific CpG sites between groups have been small, from a few percent up to 10 % [14, 16], and with few exceptions not systematically related to gene expression (e.g., [14, 17, 18])
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
