Postnatal diet remodels hepatic DNA methylation in metabolic pathways established by a maternal high-fat diet.

Abstract

We investigate how postweaning diet may modify the epigenetic landscape to meet metabolic demands later in life. Sprague-Dawley rats were exposed to a high-fat (HF) diet during gestation and lactation. At weaning, male offspring were placed either on an HF diet (HF/HF) or a control diet (HF/C). Methylation-dependent immunoprecipitation sequencing and methylation-sensitive restriction enzyme sequencing were used to quantify hepatic DNA methylation. Out of the 3966 identified differentially methylated regions, 37% were mapped to gene bodies while 6% fell within promoter or downstream regions. Differentially methylated genes were clustered in the type II diabetes mellitus and the adipocytokine signaling pathways. Our results indicate that compared with a lifelong HF diet, offspring exposed to a new postweaning control diet are able to remodel the hepatic epigenome, emphasizing the dynamic nature of the methylome even after early life.