Postweaning exposure to a high-fat diet is associated with alterations to The hepatic histone code in Japanese macaques

Melissa A. Suter, Diana Takahashi, Kevin L. Grove, Kjersti M. Aagaard

    Research output: Contribution to journalArticle

    20 Scopus citations


    Background:Expression of circadian gene, Npas2, is altered in fetal life with maternal high-fat (HF) diet exposure by virtue of alterations in The fetal histone code. We postulated that these disruptions would persist postnatally.Methods:Pregnant macaques were fed a control (CTR) or HF diet and delivered at term. When offspring were weaned, they were placed on either CTR or HF diet for a period of 5 mo to yield four exposure models (in utero diet/postweaning diet: CTR/CTR n = 5; CTR/HF n = 4; HF/CTR n = 4; and HF/HF n = 5). Liver specimens were obtained at necropsy at 1 y of age.Results:Hepatic trimethylation of lysine 4 of histone H3 is decreased (CTR/HF 0.87-fold, P = 0.038; HF/CTR 0.84-fold, P = 0.038), whereas hepatic methyltransferase activity increased by virtue of diet exposure (HF/HF 1.3-fold, P = 0.019). Using chromatin immunoprecipitation to determine Npas2 promoter occupancy, we found alterations of both repressive and permissive histone modifications specifically with postweaning HF diet exposure.Conclusion:We found that altered Npas2 expression corresponds with a change in The histone code within The Npas2 promoter.

    Original languageEnglish (US)
    Pages (from-to)252-258
    Number of pages7
    JournalPediatric Research
    Issue number3
    StatePublished - Sep 1 2013


    ASJC Scopus subject areas

    • Pediatrics, Perinatology, and Child Health

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