Molecular Metabolism (Jan 2017)

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 Binder,
  • Matthias Blüher,
  • Yvonne Böttcher

Journal volume & issue
Vol. 6, no. 1
pp. 86 – 100

Abstract

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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. Keywords: DNA methylation, Epigenetic mechanisms, Human adipose tissue depots, mRNA expression, Obesity-related co-morbidities