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Nutrients 2017, 9(4), 407; doi:10.3390/nu9040407

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

1
Department of Health and Nutritional Sciences, Box 2203, South Dakota State University, Brookings, SD 57007, USA
2
Children’s Health Research Center, Sanford Research, Sioux Falls, SD 57104, USA
3
Sanford School of Medicine-University of South Dakota, Sioux Falls, SD 57105, USA
4
Children’s Health Specialty Clinic, Sanford Children’s Hospital, Sioux Falls, SD 57117, USA
*
Authors to whom correspondence should be addressed.
Received: 18 March 2017 / Revised: 12 April 2017 / Accepted: 14 April 2017 / Published: 20 April 2017
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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. View Full-Text
Keywords: cardiometabolic disease; chromatin-immunoprecipitation sequencing; developmental programing; histone modifications; maternal high-fat diet cardiometabolic disease; chromatin-immunoprecipitation sequencing; developmental programing; histone modifications; maternal high-fat diet
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Upadhyaya, B.; Larsen, T.; Barwari, S.; Louwagie, E.J.; Baack, M.L.; Dey, M. Prenatal Exposure to a Maternal High-Fat Diet Affects Histone Modification of Cardiometabolic Genes in Newborn Rats. Nutrients 2017, 9, 407.

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