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

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

Author information

1
IFB Adiposity Diseases, University of Leipzig, Leipzig, 04103, Germany.
2
Interdisciplinary Centre for Bioinformatics, University of Leipzig, Leipzig, 04103, Germany.
3
IFB Adiposity Diseases, University of Leipzig, Leipzig, 04103, Germany; Bioinformatics Group, Department of Computer Science, University of Leipzig, 04107, Leipzig, Germany.
4
Molecular Biology Laboratory, Istituto Auxologico Italiano IRCCS, Milan, 20149, Italy.
5
Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Scania University Hospital, 205 02, Malmoe, Sweden.
6
Department of Medicine, University of Leipzig, Leipzig, 04103, Germany.
7
IFB Adiposity Diseases, University of Leipzig, Leipzig, 04103, Germany; Department of Surgery, University of Leipzig, Leipzig, 04103, Germany.
8
Städtisches Klinikum Karlsruhe, Clinic of Visceral Surgery, Karlsruhe, 76133, Germany.
9
Municipal Clinic Dresden-Neustadt, Dresden, 01129, Germany.
10
IFB Adiposity Diseases, University of Leipzig, Leipzig, 04103, Germany; Department of Medicine, University of Leipzig, Leipzig, 04103, Germany.
11
IFB Adiposity Diseases, University of Leipzig, Leipzig, 04103, Germany; Department of Medicine, University of Leipzig, Leipzig, 04103, Germany. Electronic address: matthias.blueher@medizin.uni-leipzig.de.
12
IFB Adiposity Diseases, University of Leipzig, Leipzig, 04103, Germany. Electronic address: yvonne.boettcher@medizin.uni-leipzig.de.

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

PMID:
28123940
PMCID:
PMC5220399
DOI:
10.1016/j.molmet.2016.11.003
[Indexed for MEDLINE]
Free PMC Article

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