Diabetologia

, Volume 57, Issue 11, pp 2374–2383

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

Authors

  • Maria Keller
    • Medical Faculty, IFB Adiposity DiseasesUniversity of Leipzig
  • Susan Kralisch
    • Medical Faculty, IFB Adiposity DiseasesUniversity of Leipzig
    • Department of MedicineUniversity of Leipzig
  • Kerstin Rohde
    • Medical Faculty, IFB Adiposity DiseasesUniversity of Leipzig
  • Dorit Schleinitz
    • Medical Faculty, IFB Adiposity DiseasesUniversity of Leipzig
  • Arne Dietrich
    • Medical Faculty, IFB Adiposity DiseasesUniversity of Leipzig
    • Department of SurgeryUniversity of Leipzig
  • Michael R. Schön
    • Clinic of Visceral SurgeryStädtisches Klinikum Karlsruhe
  • Daniel Gärtner
    • Clinic of Visceral SurgeryStädtisches Klinikum Karlsruhe
  • Tobias Lohmann
    • Municipal Clinic Dresden-Neustadt
  • Miriam Dreßler
    • Municipal Clinic Dresden-Neustadt
  • Anke Tönjes
    • Department of MedicineUniversity of Leipzig
  • Michael Stumvoll
    • Medical Faculty, IFB Adiposity DiseasesUniversity of Leipzig
    • Department of MedicineUniversity of Leipzig
  • Peter Kovacs
    • Medical Faculty, IFB Adiposity DiseasesUniversity of Leipzig
  • Mathias Fasshauer
    • Medical Faculty, IFB Adiposity DiseasesUniversity of Leipzig
    • Department of MedicineUniversity of Leipzig
  • Matthias Blüher
    • Department of MedicineUniversity of Leipzig
    • Medical Faculty, IFB Adiposity DiseasesUniversity of Leipzig
Article

DOI: 10.1007/s00125-014-3356-z

Cite this article as:
Keller, M., Kralisch, S., Rohde, K. et al. Diabetologia (2014) 57: 2374. doi:10.1007/s00125-014-3356-z

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 methylationEpigeneticsGlucose homeostasisHuman adipose tissueLUMASubcutaneousVisceral

Abbreviations

% 5-mC

Percentage of 5-methylcytosine

CpG

Cytosine–phosphate–guanine

DNMT

DNA methyltransferase

LINE-1

Long interspersed nuclear element

LUMA

LUminometric Based Assay

OVAT

Omental visceral adipose tissue

SAT

Subcutaneous adipose tissue

Supplementary material

125_2014_3356_MOESM1_ESM.pdf (96 kb)
ESM Methods(PDF 95 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2014