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

Mol Metab. 2016 Nov 16;6(1):86-100. doi: 10.1016/j.molmet.2016.11.003. eCollection 2017 Jan.

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.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis
  • Adipose Tissue / metabolism*
  • Aged
  • CpG Islands / genetics
  • DNA Methylation / genetics
  • Epigenesis, Genetic / genetics
  • Epigenomics
  • Female
  • Gene Expression
  • Gene Expression Profiling / methods
  • Genome-Wide Association Study
  • Humans
  • Intra-Abdominal Fat / metabolism
  • Male
  • Middle Aged
  • Obesity / genetics*
  • Promoter Regions, Genetic / genetics
  • RNA, Messenger / genetics
  • Subcutaneous Fat / metabolism

Substances

  • RNA, Messenger