title: Genome-wide DNA promoter methylation and transcriptome analysis in human adipose tissue unravels novel candidate genes for obesity.
abstract: 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-obesevs.obese individuals.
  
  
  
  We identified negatively correlated methylation and expression of several obesity-associated genes in our discovery dataset andin silicoreplicatedETV6in two independent cohorts. Further, we identified six adipose tissue depot-specific genes (HAND2,HOXC6,PPARG,SORBS2,CD36, andCLDN1). 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 thatin vitromethylation ofSORBS2directly represses gene expression.
  
  
  
  Taken together, our data show distinct tissue specific epigenetic alterations which associate with obesity.
authors.affiliation: IFB Adiposity Diseases, University of Leipzig, Leipzig, 04103, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Keller
authors.affiliation: Interdisciplinary Centre for Bioinformatics, University of Leipzig, Leipzig, 04103, Germany.
authors.forename: Lydia
authors.initials: L
authors.lastname: Hopp
authors.affiliation: IFB Adiposity Diseases, University of Leipzig, Leipzig, 04103, Germany; Bioinformatics Group, Department of Computer Science, University of Leipzig, 04107, Leipzig, Germany.
authors.forename: Xuanshi
authors.initials: X
authors.lastname: Liu
authors.affiliation: IFB Adiposity Diseases, University of Leipzig, Leipzig, 04103, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Wohland
authors.affiliation: IFB Adiposity Diseases, University of Leipzig, Leipzig, 04103, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Rohde
authors.affiliation: Molecular Biology Laboratory, Istituto Auxologico Italiano IRCCS, Milan, 20149, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Cancello
authors.affiliation: IFB Adiposity Diseases, University of Leipzig, Leipzig, 04103, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Klös
authors.affiliation: Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Scania University Hospital, 205 02, Malmoe, Sweden.
authors.forename: Karl
authors.initials: K
authors.lastname: Bacos
authors.affiliation: Department of Medicine, University of Leipzig, Leipzig, 04103, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kern
authors.affiliation: IFB Adiposity Diseases, University of Leipzig, Leipzig, 04103, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Eichelmann
authors.affiliation: IFB Adiposity Diseases, University of Leipzig, Leipzig, 04103, Germany; Department of Surgery, University of Leipzig, Leipzig, 04103, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Dietrich
authors.affiliation: Städtisches Klinikum Karlsruhe, Clinic of Visceral Surgery, Karlsruhe, 76133, Germany.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Schön
authors.affiliation: Städtisches Klinikum Karlsruhe, Clinic of Visceral Surgery, Karlsruhe, 76133, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gärtner
authors.affiliation: Municipal Clinic Dresden-Neustadt, Dresden, 01129, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Lohmann
authors.affiliation: Municipal Clinic Dresden-Neustadt, Dresden, 01129, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Dreßler
authors.affiliation: IFB Adiposity Diseases, University of Leipzig, Leipzig, 04103, Germany; Department of Medicine, University of Leipzig, Leipzig, 04103, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Stumvoll
authors.affiliation: IFB Adiposity Diseases, University of Leipzig, Leipzig, 04103, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kovacs
authors.affiliation: Molecular Biology Laboratory, Istituto Auxologico Italiano IRCCS, Milan, 20149, Italy.
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: DiBlasio
authors.affiliation: Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Scania University Hospital, 205 02, Malmoe, Sweden.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Ling
authors.affiliation: Interdisciplinary Centre for Bioinformatics, University of Leipzig, Leipzig, 04103, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Binder
authors.affiliation: 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.
authors.forename: Matthias
authors.initials: M
authors.lastname: Blüher
authors.affiliation: IFB Adiposity Diseases, University of Leipzig, Leipzig, 04103, Germany. Electronic address: yvonne.boettcher@medizin.uni-leipzig.de.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Böttcher
mesh_terms: D050156:Adipogenesis; D000273:Adipose Tissue / Q000378:metabolism*; D000368:Aged; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics; D057890:Epigenomics; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods; D055106:Genome-Wide Association Study; D006801:Humans; D050152:Intra-Abdominal Fat / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D050151:Subcutaneous Fat / Q000378:metabolism
chemical_list: D012333:RNA, Messenger
keywords: DNA methylation; Epigenetic mechanisms; Human adipose tissue depots; Obesity-related co-morbidities; mRNA expression