Obesity is associated with depot-specific alterations in adipocyte DNA methylation and gene expression

Abstract

The present study aimed to identify genes exhibiting concomitant obesity-dependent changes in DNA methylation and gene expression in adipose tissues in the mouse using diet-induced obese (DIO) C57BL/6J and genetically obese ob/ob mice as models. Mature adipocytes were isolated from epididymal and inguinal adipose tissues of ob/ob and DIO C57BL/6J mice. DNA methylation was analyzed by MeDIP-sequencing and gene expression by microarray analysis. The majority of differentially methylated regions (DMRs) were hypomethylated in obese mice. Global methylation of long interspersed elements indicated that hypomethylation did not reflect methyl donor deficiency. In both DIO and ob/ob mice, we observed more obesity-associated methylation changes in epididymal than in inguinal adipocytes. Assignment of DMRs to promoter, exon, intron and intergenic regions demonstrated that DIO-induced changes in DNA methylation in C57BL/6J mice occurred primarily in exons, whereas inguinal adipocytes of ob/ob mice exhibited a higher enrichment of DMRs in promoter regions than in other regions of the genome, suggesting an influence of leptin on DNA methylation in inguinal adipocytes. We observed altered methylation and expression of 9 genes in epididymal adipocytes, including the known obesity-associated genes, Ehd2 and Kctd15, and a novel candidate gene, Irf8, possibly involved in immune type 1/type2 balance. The use of 2 obesity models enabled us to dissociate changes associated with high fat feeding from those associated with obesity per se. This information will be of value in future studies on the mechanisms governing the development of obesity and changes in adipocyte function associated with obesity.

Computational analyses of obesity associated loci generated by genome-wide association studies

“…Variants of the KCTD15 were associated with risk for obesity. In adipose tissues of 2 obesity mice models, KCTD15 exhibited concomitant obesity-dependent alterations in DNA methylation and gene expression [ 14 ]. MTCH2 is a conserved regulator of lipid homeostasis.…”

EHD2-mediated restriction of caveolar dynamics regulates cellular lipid uptake

“…Remarkably, the expression levels of EHD2 in WAT from obese patients as well as in WAT of two obese mouse models (ob/ob and NZO mice) and of EHD2 del/+ mice treated with a long-term high fat diet were significantly reduced. Thus, expression of EHD2 appears to negatively correlate with adipocyte size, therefore reflecting the situation in the EHD2 KO mouse (see also (46)). We speculate that an imbalance in number, life-time and mobility of caveolae may accompany and possibly actively contribute to the development and progression of obesity.…”

Antiobesity Potential of Fresh Cow Urine and its Distillate - A Biomedicine for Tomorrow

“…21,22 The HFD induced obesity is known to be the most significant model for the assessment of anti-obesity activity because of its close resemblance of copycatting the usual route of obesity episodes in human beings. 23,24 Thus, in the present study high-fat diet was given for 2 months to the Wistar rats for induction of obesity to develop the experimental model to be utilized for the assessment of anti-obesity activity. It is well established that over-consumption food along with the high concentration of fat lead to obesity in several animal's models including rats due to metabolic complications as well as liver dysfunction.…”