title: Prolonged high-fat diet induces gradual and fat depot-specific DNA methylation changes in adult mice.
abstract: High-fat diets (HFD) are thought to contribute to the development of metabolism-related diseases. The long-term impact of HFD may be mediated by epigenetic mechanisms, and indeed, HFD has been reported to induce DNA methylation changes in white adipose tissue (WAT) near metabolism related genes. However, previous studies were limited to a single WAT depot, a single time-point and primarily examined the pre-pubertal period. To define dynamic DNA methylation patterns specific for WAT depots, we investigated DNA methylation of Pparg2 and Leptin in gonadal adipose tissue (GAT) and subcutaneous adipose tissue (SAT), at baseline and after 6, 12 and 24 weeks of HFD exposure in adult mice. HFD induced hypermethylation of both the Leptin promoter (max. 19.6% at week 24, P = 2.6·10-3) and the Pparg2 promoter in GAT (max. 10.5% at week 12, P = 0.001). The differential methylation was independent of immune cell infiltration upon HFD exposure. In contrast, no differential methylation in the Pparg2 and Leptin promoter was observed in SAT. Leptin and Pparg2 DNA methylation were correlated with gene expression in GAT. Our study shows that prolonged exposure to HFD in adulthood is associated with a gradually increasing DNA methylation level at the Leptin and Pparg2 promoters in a depot-specific manner.
authors.affiliation: Molecular Epidemiology section, Leiden University Medical Center, The Netherlands.
authors.forename: Ramona A J
authors.initials: RA
authors.lastname: Zwamborn
authors.affiliation: Molecular Epidemiology section, Leiden University Medical Center, The Netherlands.
authors.forename: Roderick C
authors.initials: RC
authors.lastname: Slieker
authors.affiliation: Department of Metabolic Health Research, TNO, Leiden, The Netherlands.|Department of Vascular Surgery, Leiden University Medical Center, The Netherlands.
authors.forename: Petra C A
authors.initials: PC
authors.lastname: Mulder
authors.affiliation: Molecular Epidemiology section, Leiden University Medical Center, The Netherlands.
authors.forename: Inge
authors.initials: I
authors.lastname: Zoetemelk
authors.affiliation: Department of Microbiology &Systems Biology, TNO, Zeist, The Netherlands.
authors.forename: Lars
authors.initials: L
authors.lastname: Verschuren
authors.affiliation: Molecular Epidemiology section, Leiden University Medical Center, The Netherlands.
authors.forename: H Eka D
authors.initials: HE
authors.lastname: Suchiman
authors.affiliation: Department of Metabolic Health Research, TNO, Leiden, The Netherlands.
authors.forename: Karin H
authors.initials: KH
authors.lastname: Toet
authors.affiliation: Department of Metabolic Health Research, TNO, Leiden, The Netherlands.
authors.forename: Simone
authors.initials: S
authors.lastname: Droog
authors.affiliation: Molecular Epidemiology section, Leiden University Medical Center, The Netherlands.
authors.forename: P Eline
authors.initials: PE
authors.lastname: Slagboom
authors.affiliation: Department of Metabolic Health Research, TNO, Leiden, The Netherlands.
authors.forename: Teake
authors.initials: T
authors.lastname: Kooistra
authors.affiliation: Department of Metabolic Health Research, TNO, Leiden, The Netherlands.|Department of Vascular Surgery, Leiden University Medical Center, The Netherlands.
authors.forename: Robert
authors.initials: R
authors.lastname: Kleemann
authors.affiliation: Molecular Epidemiology section, Leiden University Medical Center, The Netherlands.
authors.forename: Bastiaan T
authors.initials: BT
authors.lastname: Heijmans
mesh_terms: D052436:Adipose Tissue, White / Q000473:pathology*; D000818:Animals; D019175:DNA Methylation; D059305:Diet, High-Fat; D044127:Epigenesis, Genetic; D006066:Gonads / Q000473:pathology; D020738:Leptin / Q000235:genetics*; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000235:genetics*; D011401:Promoter Regions, Genetic; D040521:Subcutaneous Tissue / Q000473:pathology; D013997:Time Factors
chemical_list: D020738:Leptin; D047495:PPAR gamma