Am J Obstet Gynecol

ObjectiveData from animal models show that in utero exposure to a maternal high fat diet (HFD) renders susceptibility of these offspring to the adult onset of metabolic syndrome. We and others have previously shown that epigenetic modifications to histones may serve as a molecular memory of the in utero exposure, rendering risk of adult disease. Because mice heterozygous for GLUT4 (insulin sensitive glucose transporter) born to wild-type (WT) mothers demonstrate exacterbated metabolic syndrome when exposed to a high fat diet in utero, we sought to analyze the genome-wide epigenetic changes which occur in the fetal liver in susceptible offspring.Study DesignWT and Glut4+/\ue2\u2c6\u2019 (G4+/\ue2\u2c6\u2019) offspring of WT mothers exposed either to a control or a HF diet in utero were studied. Immunoblotting was used to measure hepatic histone modifications of fetal and 5 week animals. Chromatin immunoprecipitation (ChIP) followed by hybridization to chip arrays (ChIP on chip) was utilized to detect genome-wide changes of histone modifications with HFD exposure.ResultsWe found that levels of hepatic H3K14ac and H3K9me3 significantly increased with HFD exposure in WT and G4+/\ue2\u2c6\u2019 fetal and 5 week offspring. Pathway analysis of our ChIP on chip data reveal differential H3K14ac and H3K9me3 enrichment along pathways which regulate lipid metabolism, specifically in the promoter regions of Pparg, Ppara, Rxra and Rora.ConclusionWe conclude that HFD exposure in utero is associated with functional alterations to fetal hepatic histone modifications in both WT and G4+/\ue2\u2c6\u2019 offspring, some which persist up to 5 weeks of age.DP2 OD001500/OD/NIH HHS/United StatesDP2O D001500-01/DP/NCCDPHP CDC HHS/United StatesK12 GM084897/GM/NIGMS NIH HHS/United StatesK12 GM084897/GM/NIGMS NIH HHS/United StatesL40 HD051105/HD/NICHD NIH HHS/United StatesP30 DK056338/DK/NIDDK NIH HHS/United StatesP60 DK020541/DK/NIDDK NIH HHS/United StatesR01 DK089201/DK/NIDDK NIH HHS/United StatesR01 DK089201/DK/NIDDK NIH HHS/United StatesR21 DK081194/DK/NIDDK NIH HHS/United States2015-05-01T00:00:00Z24793723PMC436844