Scientific reports | 03-03-2017 |


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.

Auteurs: Zwamborn RA1, Slieker RC1, Mulder PC2,3, Zoetemelk I1, Verschuren L4, Suchiman HE1, Toet KH2, Droog S2, Slagboom PE1, Kooistra T2, Kleemann R2,3, Heijmans BT1.

 Affiliations: 1Molecular Epidemiology section, Leiden University Medical Center, The Netherlands. 2Department of Metabolic Health Research, TNO, Leiden, The Netherlands. 3Department of Vascular Surgery, Leiden University Medical Center, The Netherlands. 4Department of Microbiology &Systems Biology, TNO, Zeist, The Netherlands.