Elsevier

Molecular Metabolism

Volume 6, Issue 1, January 2017, Pages 86-100
Molecular Metabolism

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

https://doi.org/10.1016/j.molmet.2016.11.003Get rights and content
Under a Creative Commons license
open access

Highlights

  • Obesity-associated differences in DNA promoter methylation and transcriptome in human adipose tissue (ETV6).

  • Depot-specific analyses revealed novel/known genes (HAND2, HOXC6, PPARG, SORBS2, CD36, CLDN1).

  • EWAS revealed SSPN and CCDC125 associated to BMI in SAT or OVAT, respectively.

  • Differentially methylated genes overlap in part with GWAS hits for obesity and fat distribution.

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
mRNA expression
Obesity-related co-morbidities

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Permanent address: University of Oslo, Institute of Clinical Medicine, Akershus University Hospital, 1478, Lørenskog, Norway.