Prenatal exposure to a maternal High-Fat diet affects histone modification of cardiometabolic genes in newborn rats

Bijaya Upadhyaya, Tricia Larsen, Shivon Barwari, Eli J. Louwagie, Michelle L. Baack, Moul Dey

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Infants born to women with diabetes or obesity are exposed to excess circulating fuels during fetal heart development and are at higher risk of cardiac diseases. We have previously shown that late-gestation diabetes, especially in conjunction with a maternal high-fat (HF) diet, impairs cardiac functions in rat-offspring. This study investigated changes in genome-wide histone modifications in newborn hearts from rat-pups exposed to maternal diabetes and HF-diet. Chromatin-immunoprecipitation-sequencing revealed a differential peak distribution on gene promoters in exposed pups with respect to acetylation of lysines 9 and 14 and to trimethylation of lysines 4 and 27 in histone H3 (all, false discovery rate, FDR < 0.1). In the HF-diet exposed offspring, 54% of the annotated genes showed the gene-activating mark trimethylated lysine 4. Many of these genes (1) are associated with the “metabolic process” in general and particularly with “positive regulation of cholesterol biosynthesis” (FDR = 0.03), (2) overlap with 455 quantitative trait loci for blood pressure, body weight, serum cholesterol (all, FDR < 0.1), and (3) are linked to cardiac disease susceptibility/progression, based on disease ontology analyses and scientific literature. These results indicate that maternal HF-diet changes the cardiac histone signature in offspring suggesting a fuel-mediated epigenetic reprogramming of cardiac tissue in utero.

Original languageEnglish (US)
Article number407
JournalNutrients
Volume9
Issue number4
DOIs
StatePublished - Apr 20 2017

Keywords

  • Cardiometabolic disease
  • Chromatin-immunoprecipitation sequencing
  • Developmental programing
  • Histone modifications
  • Maternal high-fat diet

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics

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