TY - JOUR
T1 - Genome-wide DNA promoter methylation and transcriptome analysis in human adipose tissue unravels novel candidate genes for obesity
AU - Keller, Maria
AU - Hopp, Lydia
AU - Liu, Xuanshi
AU - Wohland, Tobias
AU - Rohde, Kerstin
AU - Cancello, Raffaella
AU - Klös, Matthias
AU - Bacos, Karl
AU - Kern, Matthias
AU - Eichelmann, Fabian
AU - Dietrich, Arne
AU - Schön, Michael R.
AU - Gärtner, Daniel
AU - Lohmann, Tobias
AU - Dreßler, Miriam
AU - Stumvoll, Michael
AU - Kovacs, Peter
AU - DiBlasio, Anna Maria
AU - Ling, Charlotte
AU - Binder, Hans
AU - Blüher, Matthias
AU - Böttcher, Yvonne
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
KW - DNA methylation
KW - Epigenetic mechanisms
KW - Human adipose tissue depots
KW - mRNA expression
KW - Obesity-related co-morbidities
UR - http://www.scopus.com/inward/record.url?scp=85007405955&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85007405955&partnerID=8YFLogxK
U2 - 10.1016/j.molmet.2016.11.003
DO - 10.1016/j.molmet.2016.11.003
M3 - Article
AN - SCOPUS:85007405955
VL - 6
SP - 86
EP - 100
JO - Molecular Metabolism
JF - Molecular Metabolism
SN - 2212-8778
IS - 1
ER -