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

Keller, Maria LU ; Hopp, Lydia; Liu, Xuanshi; Wohland, Tobias; Rohde, Kerstin LU ; Cancello, Raffaella; Klös, Matthias; Bacos, Karl LU ; Kern, Matthias and Eichelmann, Fabian, et al. (2017) In Molecular Metabolism 6(1). p.86-100
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... (More)

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.

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publication status
published
subject
keywords
DNA methylation, Epigenetic mechanisms, Human adipose tissue depots, mRNA expression, Obesity-related co-morbidities
in
Molecular Metabolism
volume
6
issue
1
pages
15 pages
publisher
Elsevier GmbH
external identifiers
  • scopus:85007405955
  • wos:000396209100012
ISSN
2212-8778
DOI
10.1016/j.molmet.2016.11.003
language
English
LU publication?
yes
id
02537b4b-56d2-4f38-9189-f1f95be785f4
date added to LUP
2017-03-24 11:31:02
date last changed
2018-01-21 04:20:27
@article{02537b4b-56d2-4f38-9189-f1f95be785f4,
  abstract     = {<p>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.</p>},
  author       = {Keller, Maria and Hopp, Lydia and Liu, Xuanshi and Wohland, Tobias and Rohde, Kerstin and Cancello, Raffaella and Klös, Matthias and Bacos, Karl and Kern, Matthias and Eichelmann, Fabian and Dietrich, Arne and Schön, Michael R. and Gärtner, Daniel and Lohmann, Tobias and Dreßler, Miriam and Stumvoll, Michael and Kovacs, Peter and DiBlasio, Anna Maria and Ling, Charlotte and Binder, Hans and Blüher, Matthias and Böttcher, Yvonne},
  issn         = {2212-8778},
  keyword      = {DNA methylation,Epigenetic mechanisms,Human adipose tissue depots,mRNA expression,Obesity-related co-morbidities},
  language     = {eng},
  month        = {01},
  number       = {1},
  pages        = {86--100},
  publisher    = {Elsevier GmbH},
  series       = {Molecular Metabolism},
  title        = {Genome-wide DNA promoter methylation and transcriptome analysis in human adipose tissue unravels novel candidate genes for obesity},
  url          = {http://dx.doi.org/10.1016/j.molmet.2016.11.003},
  volume       = {6},
  year         = {2017},
}