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Nutrients. 2017 Apr 20;9(4). pii: E407. doi: 10.3390/nu9040407.

Prenatal Exposure to a Maternal High-Fat Diet Affects Histone Modification of Cardiometabolic Genes in Newborn Rats.

Author information

1
Department of Health and Nutritional Sciences, Box 2203, South Dakota State University, Brookings, SD 57007, USA. bupadhyaya2@unl.edu.
2
Children's Health Research Center, Sanford Research, Sioux Falls, SD 57104, USA. Tricia.Larsen@SanfordHealth.org.
3
Department of Health and Nutritional Sciences, Box 2203, South Dakota State University, Brookings, SD 57007, USA. shivon.barwari@jacks.sdstate.edu.
4
Sanford School of Medicine-University of South Dakota, Sioux Falls, SD 57105, USA. Eli.Louwagie@sanfordhealth.org.
5
Children's Health Research Center, Sanford Research, Sioux Falls, SD 57104, USA. michelle.baack@sanfordhealth.org.
6
Sanford School of Medicine-University of South Dakota, Sioux Falls, SD 57105, USA. michelle.baack@sanfordhealth.org.
7
Children's Health Specialty Clinic, Sanford Children's Hospital, Sioux Falls, SD 57117, USA. michelle.baack@sanfordhealth.org.
8
Department of Health and Nutritional Sciences, Box 2203, South Dakota State University, Brookings, SD 57007, USA. Moul.Dey@sdstate.edu.

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.

KEYWORDS:

cardiometabolic disease; chromatin-immunoprecipitation sequencing; developmental programing; histone modifications; maternal high-fat diet

PMID:
28425976
PMCID:
PMC5409746
DOI:
10.3390/nu9040407
[Indexed for MEDLINE]
Free PMC Article

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