Diabetologia

, Volume 57, Issue 11, pp 2374–2383

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

  • Maria Keller
  • Susan Kralisch
  • Kerstin Rohde
  • Dorit Schleinitz
  • Arne Dietrich
  • Michael R. Schön
  • Daniel Gärtner
  • Tobias Lohmann
  • Miriam Dreßler
  • Anke Tönjes
  • Michael Stumvoll
  • Peter Kovacs
  • Mathias Fasshauer
  • Matthias Blüher
  • Yvonne Böttcher
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

Authors and Affiliations

  • Maria Keller
    • 1
  • Susan Kralisch
    • 1
    • 2
  • Kerstin Rohde
    • 1
  • Dorit Schleinitz
    • 1
  • Arne Dietrich
    • 1
    • 3
  • Michael R. Schön
    • 4
  • Daniel Gärtner
    • 4
  • Tobias Lohmann
    • 5
  • Miriam Dreßler
    • 5
  • Anke Tönjes
    • 2
  • Michael Stumvoll
    • 1
    • 2
  • Peter Kovacs
    • 1
  • Mathias Fasshauer
    • 1
    • 2
  • Matthias Blüher
    • 2
  • Yvonne Böttcher
    • 1
  1. 1.Medical Faculty, IFB Adiposity DiseasesUniversity of LeipzigLeipzigGermany
  2. 2.Department of MedicineUniversity of LeipzigLeipzigGermany
  3. 3.Department of SurgeryUniversity of LeipzigLeipzigGermany
  4. 4.Clinic of Visceral SurgeryStädtisches Klinikum KarlsruheKarlsruheGermany
  5. 5.Municipal Clinic Dresden-NeustadtDresdenGermany