Global DNA methylation levels in human adipose tissue are related to fat distribution and glucose homeostasis

Aims/hypothesis Epigenetic alterations may influence the metabolic pathways involved in human obesity. We hypothesised that global DNA methylation levels in adipose tissue might be associated with obesity and related phenotypes. Methods We measured global DNA methylation levels in paired samples of subcutaneous adipose tissue (SAT) and omental visceral adipose tissue (OVAT) from 51 individuals, and in leucocytes from 559 Sorbs, a population from Germany, using LUminometric Methylation Assay (LUMA). To further investigate the underlying mechanisms of the observed associations, we measured global methylation levels in 3T3-L1 adipocytes exposed to glucose, insulin and lipids. Results Global methylation levels (+/- SD) were significantly higher in OVAT (74.27%+/- 2.2%) compared with SAT (71.97%+/- 2.4%; paired t test, p<1 x 10(-9)). Furthermore, global methylation levels in SAT were positive correlates of measures of fat distribution (waist measurement, WHR) and glucose homeostasis (HbA(1c)) (all p<0.015 after accounting for multiple testing and covariates). Global methylation levels in the German Sorb cohort were associated with glucose homeostasis, but this association did not withstand adjustment for covariates. Exposure of 3T3-L1 adipocytes to insulin, palmitate and glucose decreased global methylation levels 1 h after treatment relative to controls. Conclusions/interpretation Our data suggest that the variability in global methylation in adipose tissue might be related to alterations in glucose metabolism.