title: Global DNA methylation levels in human adipose tissue are related to fat distribution and glucose homeostasis.
abstract: OBJECTIVE
  Epigenetic alterations may influence the metabolic pathways involved in human obesity. We hypothesised that global DNA methylation levels in adipose tissue might be associated with obesity and related phenotypes.
  
  
  METHODS
  We measured global DNA methylation levels in paired samples of subcutaneous adipose tissue (SAT) and omental visceral adipose tissue (OVAT) from 51 individuals, and in leucocytes from 559 Sorbs, a population from Germany, using LUminometric Methylation Assay (LUMA). To further investigate the underlying mechanisms of the observed associations, we measured global methylation levels in 3T3-L1 adipocytes exposed to glucose, insulin and lipids.
  
  
  RESULTS
  Global methylation levels (±SD) were significantly higher in OVAT (74.27% ± 2.2%) compared with SAT (71.97% ± 2.4%; paired t test, p < 1 × 10(-9)). Furthermore, global methylation levels in SAT were positive correlates of measures of fat distribution (waist measurement, WHR) and glucose homeostasis (HbA1c) (all p < 0.015 after accounting for multiple testing and covariates). Global methylation levels in the German Sorb cohort were associated with glucose homeostasis, but this association did not withstand adjustment for covariates. Exposure of 3T3-L1 adipocytes to insulin, palmitate and glucose decreased global methylation levels 1 h after treatment relative to controls.
  
  
  CONCLUSIONS
  Our data suggest that the variability in global methylation in adipose tissue might be related to alterations in glucose metabolism.
authors.affiliation: Medical Faculty, IFB Adiposity Diseases, University of Leipzig, Liebigstrasse 21, 04103, Leipzig, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Keller
authors.forename: Susan
authors.initials: S
authors.lastname: Kralisch
authors.forename: Kerstin
authors.initials: K
authors.lastname: Rohde
authors.forename: Dorit
authors.initials: D
authors.lastname: Schleinitz
authors.forename: Arne
authors.initials: A
authors.lastname: Dietrich
authors.forename: Michael R
authors.initials: MR
authors.lastname: Schön
authors.forename: Daniel
authors.initials: D
authors.lastname: Gärtner
authors.forename: Tobias
authors.initials: T
authors.lastname: Lohmann
authors.forename: Miriam
authors.initials: M
authors.lastname: Dreßler
authors.forename: Anke
authors.initials: A
authors.lastname: Tönjes
authors.forename: Michael
authors.initials: M
authors.lastname: Stumvoll
authors.forename: Peter
authors.initials: P
authors.lastname: Kovacs
authors.forename: Mathias
authors.initials: M
authors.lastname: Fasshauer
authors.forename: Matthias
authors.initials: M
authors.lastname: Blüher
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Böttcher
mesh_terms: D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D019175:DNA Methylation / Q000502:physiology*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D050152:Intra-Abdominal Fat / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged
chemical_list: D005947:Glucose