Article

Diabetologia

, Volume 57, Issue 11, pp 2374-2383

First online:

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

  • Maria KellerAffiliated withMedical Faculty, IFB Adiposity Diseases, University of Leipzig
  • , Susan KralischAffiliated withMedical Faculty, IFB Adiposity Diseases, University of LeipzigDepartment of Medicine, University of Leipzig
  • , Kerstin RohdeAffiliated withMedical Faculty, IFB Adiposity Diseases, University of Leipzig
  • , Dorit SchleinitzAffiliated withMedical Faculty, IFB Adiposity Diseases, University of Leipzig
  • , Arne DietrichAffiliated withMedical Faculty, IFB Adiposity Diseases, University of LeipzigDepartment of Surgery, University of Leipzig
  • , Michael R. SchönAffiliated withClinic of Visceral Surgery, Städtisches Klinikum Karlsruhe
  • , Daniel GärtnerAffiliated withClinic of Visceral Surgery, Städtisches Klinikum Karlsruhe
  • , Tobias LohmannAffiliated withMunicipal Clinic Dresden-Neustadt
  • , Miriam DreßlerAffiliated withMunicipal Clinic Dresden-Neustadt
    • , Anke TönjesAffiliated withDepartment of Medicine, University of Leipzig
    • , Michael StumvollAffiliated withMedical Faculty, IFB Adiposity Diseases, University of LeipzigDepartment of Medicine, University of Leipzig
    • , Peter KovacsAffiliated withMedical Faculty, IFB Adiposity Diseases, University of Leipzig
    • , Mathias FasshauerAffiliated withMedical Faculty, IFB Adiposity Diseases, University of LeipzigDepartment of Medicine, University of Leipzig
    • , Matthias BlüherAffiliated withDepartment of Medicine, University of Leipzig
    • , Yvonne BöttcherAffiliated withMedical Faculty, IFB Adiposity Diseases, University of Leipzig Email author 

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Abstract

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 × 10−9). Furthermore, global methylation levels in SAT were positive correlates of measures of fat distribution (waist measurement, WHR) and glucose homeostasis (HbA1c) (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.

Keywords

DNA methylation Epigenetics Glucose homeostasis Human adipose tissue LUMA Subcutaneous Visceral