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Am J Obstet Gynecol. 2014 May;210(5):463.e1-463.e11. doi: 10.1016/j.ajog.2014.01.045.

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

Author information

1
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX.
2
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY; Division of Pediatric Endocrinology, Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY.
3
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY.
4
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY; Department of Medicine, Albert Einstein College of Medicine, Bronx, NY; Department of Obstetrics and Gynecology and Women's Health, Albert Einstein College of Medicine, Bronx, NY.
5
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX. Electronic address: aagaardt@bcm.tmc.edu.

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.

KEYWORDS:

GLUT4; H3K14ac; H3K9me3; developmental origin

PMID:
24793723
PMCID:
PMC4368445
DOI:
10.1016/j.ajog.2014.01.045
[Indexed for MEDLINE]
Free PMC Article

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