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

• Published in: Nutrients Vol. 9; no. 4; p. 407
• Main Authors: Upadhyaya, Bijaya, Larsen, Tricia, Barwari, Shivon, Louwagie, Eli J, Baack, Michelle L, Dey, Moul
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20.04.2017; MDPI
• Subjects: Acetylation; Animals; Animals, Newborn; Biosynthesis; Blood Pressure; Body Weight; cardiometabolic disease; Cardiovascular Diseases - etiology; Cardiovascular Diseases - genetics; Cholesterol; Cholesterol - blood; Chromatin; chromatin-immunoprecipitation sequencing; Coronary artery disease; developmental programing; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental; Diet, High-Fat - adverse effects; Epigenesis, Genetic; Epigenetics; Exposure; Female; Fetal Development; Fetuses; Gene Expression Regulation, Developmental; Genes; Genetic Association Studies; Genetic Predisposition to Disease; Genomes; Gestation; Health risks; Heart diseases; High fat diet; Histone Code; Histone H3; histone modifications; Immunoprecipitation; Infants; Lysine; maternal high-fat diet; Maternal Nutritional Physiological Phenomena; Metabolic Syndrome - etiology; Metabolic Syndrome - genetics; Offspring; Pregnancy; Prenatal experience; Prenatal exposure; Prenatal Exposure Delayed Effects - genetics; Promoter Regions, Genetic; Promoters; Quantitative Trait Loci; Rats; Rats, Sprague-Dawley; Rodents; Sequence Analysis, DNA; developmental programing; histone modifications; cardiometabolic disease; maternal high-fat diet; chromatin-immunoprecipitation sequencing
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu9040407

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.