Genome-wide DNA promoter methylation and transcriptome analysis in human adipose tissue unravels novel candidate genes for obesity

Maria Keller, Lydia Hopp, Xuanshi Liu, Tobias Wohland, Kerstin Rohde, Raffaella Cancello, Matthias Klös, Karl Bacos, Matthias Kern, Fabian Eichelmann, Arne Dietrich, Michael R. Schön, Daniel Gärtner, Tobias Lohmann, Miriam Dreßler, Michael Stumvoll, Peter Kovacs, Anna Maria DiBlasio, Charlotte Ling, Hans BinderMatthias Blüher, Yvonne Böttcher

Research output: Contribution to journalArticle

Abstract

Objective/methods DNA methylation plays an important role in obesity and related metabolic complications. We examined genome-wide DNA promoter methylation along with mRNA profiles in paired samples of human subcutaneous adipose tissue (SAT) and omental visceral adipose tissue (OVAT) from non-obese vs. obese individuals. Results We identified negatively correlated methylation and expression of several obesity-associated genes in our discovery dataset and in silico replicated ETV6 in two independent cohorts. Further, we identified six adipose tissue depot-specific genes (HAND2, HOXC6, PPARG, SORBS2, CD36, and CLDN1). The effects were further supported in additional independent cohorts. Our top hits might play a role in adipogenesis and differentiation, obesity, lipid metabolism, and adipose tissue expandability. Finally, we show that in vitro methylation of SORBS2 directly represses gene expression. Conclusions Taken together, our data show distinct tissue specific epigenetic alterations which associate with obesity.

Original languageEnglish
Pages (from-to)86-100
Number of pages15
JournalMolecular Metabolism
Volume6
Issue number1
DOIs
Publication statusPublished - Jan 1 2017

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Keywords

  • DNA methylation
  • Epigenetic mechanisms
  • Human adipose tissue depots
  • mRNA expression
  • Obesity-related co-morbidities

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Keller, M., Hopp, L., Liu, X., Wohland, T., Rohde, K., Cancello, R., Klös, M., Bacos, K., Kern, M., Eichelmann, F., Dietrich, A., Schön, M. R., Gärtner, D., Lohmann, T., Dreßler, M., Stumvoll, M., Kovacs, P., DiBlasio, A. M., Ling, C., ... Böttcher, Y. (2017). Genome-wide DNA promoter methylation and transcriptome analysis in human adipose tissue unravels novel candidate genes for obesity. Molecular Metabolism, 6(1), 86-100. https://doi.org/10.1016/j.molmet.2016.11.003