Title
Prolonged high-fat diet induces gradual and fat depot-specific DNA methylation changes in adult mice
Author
Slieker, R.C.
Mulder, P.C.A.
Zoetemelk, I.
Verschuren, L.
Suchiman, H.E.D.
Toet, K.H.
Droog, S.
Slagboom, P.E.
Kooistra, T.
Kleemann, R.
Heijmans, B.T.
Publication year
2017
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.
Subject
ELSS - Earth, Life and Social Sciences
Life
Healthy Living
Biomedical Innovation
Biology
MHR - Metabolic Health Research MSB - Microbiology and Systems Biology
To reference this document use:
http://resolver.tudelft.nl/uuid:be711dea-227a-4a77-ac40-8849d5336d45
DOI
https://doi.org/10.1038/srep43261
TNO identifier
745888
Source
Scientific Reports
Document type
article