In utero exposure to a maternal high-fat diet alters the epigenetic histone code in a murine model

Melissa A. Suter, Jun Ma, Patricia M. Vuguin, Kirsten Hartil, Ariana Fiallo, R. Alan Harris, Maureen J. Charron, Kjersti M. Aagaard

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Abstract

Objective Data 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 the risk of adult disease. Because mice heterozygous for the Glut4 gene (insulin sensitive glucose transporter) born to wild-type (WT) mothers demonstrate exacterbated metabolic syndrome when exposed to an HFD in utero, we sought to analyze the genome-wide epigenetic changes that occur in the fetal liver in susceptible offspring. Study Design WT and Glut4+/- (G4+/-) offspring of WT mothers that were exposed either to a control or an HFD 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 used to detect genome-wide changes of histone modifications with HFD exposure. Results We found that levels of hepatic H3K14ac and H3K9me3 significantly increased with HFD exposure in WT and G4+/- fetal and 5-week offspring. Pathway analysis of our ChIP-on-chip data revealed differential H3K14ac and H3K9me3 enrichment along pathways that regulate lipid metabolism, specifically in the promoter regions of Pparg, Ppara, Rxra, and Rora. Conclusion We conclude that HFD exposure in utero is associated with functional alterations to fetal hepatic histone modifications in both WT and G4+/- offspring, some of which persist up to 5 weeks of age.

Original languageEnglish (US)
Pages (from-to)463.e1-463.e11
JournalAmerican journal of obstetrics and gynecology
Volume210
Issue number5
DOIs
StatePublished - May 2014

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Keywords

  • GLUT4
  • H3K14ac
  • H3K9me3
  • developmental origin

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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