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

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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.

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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

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Acknowledgements

We thank all those who participated in the studies. We are grateful to U. Lössner, I. Müller, M. Prellberg, M. Kern and M. Klös for excellent technical assistance and A. Crane for English language editing.

Funding

This work was supported by grants from the German Diabetes Association (to YB and PK) and from the DDS Foundation to YB and SK. YB was further supported by a research grant from the IFB AdiposityDiseases ADI-K50D, K7-45 and by a research fellowship from the EFSD (European Foundation for the Study of Diabetes). MK was funded by ADI-K7-39. MF was supported by K7-3, K7-9 and K7-31, and PK by ADI-K60E. IFB AdiposityDiseases is supported by the Federal Ministry of Education and Research (BMBF), Germany, FKZ: 01EO1001. DS and PK are funded by a research grant from the Boehringer Ingelheim Foundation. This work was further supported by the Kompetenznetz Adipositas (Competence Network for Obesity) funded by the Federal Ministry of Education and Research (German Obesity Biomaterial Bank; FKZ 01GI1128), a grant from Deutsche Forschungsgemeinschaft the SFB 1052/1: ‘Obesity mechanisms’ (projects C01, C06, B01; B03) (to AT, MF, MB and PK, respectively) and a research grant BO 3147/4-1 to YB. This work is supported by LIFE–Leipzig Research Center for Civilization Diseases, University of Leipzig. LIFE is funded by the European Union, the European Regional Development Fund (ERDF) and the Free State of Saxony within the framework of the excellence initiative. The work was supported by the Deutsche Hochdruckliga e.V. (to MF).

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Contribution statement

MK and YB were responsible for conception and design of the study. SK, AD, MRS, DG, TL, MD, AT, MS, MF and MB contributed to the acquisition of data. MK, SK, KR, DS, PK, MB and YB contributed to analysis and interpretation of the data. MK and YB were responsible for drafting the manuscript. All authors revised the manuscript critically for important intellectual content and approved the final version. MK and YB are the guarantors of this work.

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Authors and Affiliations

  1. Medical Faculty, IFB Adiposity Diseases, University of Leipzig, Liebigstrasse 21, 04103, Leipzig, Germany

    Maria Keller, Susan Kralisch, Kerstin Rohde, Dorit Schleinitz, Arne Dietrich, Michael Stumvoll, Peter Kovacs, Mathias Fasshauer & Yvonne Böttcher

  2. Department of Medicine, University of Leipzig, Leipzig, Germany

    Susan Kralisch, Anke Tönjes, Michael Stumvoll, Mathias Fasshauer & Matthias Blüher

  3. Department of Surgery, University of Leipzig, Leipzig, Germany

    Arne Dietrich

  4. Clinic of Visceral Surgery, Städtisches Klinikum Karlsruhe, Karlsruhe, Germany

    Michael R. Schön & Daniel Gärtner

  5. Municipal Clinic Dresden-Neustadt, Dresden, Germany

    Tobias Lohmann & Miriam Dreßler

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  1. Maria Keller
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Correspondence to Yvonne Böttcher.

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Keller, M., Kralisch, S., Rohde, K. et al. Global DNA methylation levels in human adipose tissue are related to fat distribution and glucose homeostasis. Diabetologia 57, 2374–2383 (2014). https://doi.org/10.1007/s00125-014-3356-z

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  • DOI: https://doi.org/10.1007/s00125-014-3356-z

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