Dietary Unsaturated Fatty Acids Modulate Maternal Dyslipidemia-Induced DNA Methylation and Histone Acetylation in Placenta and Fetal Liver in Rats.

The present study assessed the role of dietary unsaturated fatty acids in maternal dyslipidemia-induced DNA methylation and histone acetylation in placenta and fetal liver and accumulation of lipids in the fetal liver. Weanling female Wistar rats were fed control and experimental diets for 2 months, mated, and continued on their diets during pregnancy. At gestation days of 18-20, rats were euthanized to isolate placenta and fetal liver. DNA methylation, DNA methyl transferase-1 (DNMT1) activity, acetylation of histones (H2A and H2B), and histone acyl transferase (HAT) activity were evaluated in placenta and fetal liver. Fetal liver lipid accumulation and activation of peroxisome proliferator-activated receptor-α (PPAR-α) were assessed. Maternal dyslipidemia caused significant epigenetic changes in placenta and fetal liver. In the placenta, (1) global DNA methylation increased by 37% and DNMT1 activity by 86%, (2) acetylated H2A and H2B levels decreased by 46% and 24% respectively, and (3) HAT activity decreased by 39%. In fetal liver, (1) global DNA methylation increased by 52% and DNMT1 activity by 78%, (2) acetylated H2A and H2B levels decreased by 28% and 26% respectively, and (3) HAT activity decreased by 37%. Maternal dyslipidemia caused a 4.75-fold increase in fetal liver triacylglycerol accumulation with a 78% decrease in DNA-binding ability of PPAR-α. Incorporation of dietary unsaturated fatty acids in the maternal high-fat diet significantly (p < 0.05) modulated dyslipidemia-induced effects in placenta and fetal liver. Eicosapentaenoic acid (EPA, 20:5n-3) + docosahexaenoic acid (DHA, 22:6n-3) exhibited a profound effect followed by alpha-linolenic acid (ALA, 18:3n-3) than linoleic acid (LNA, 18:2n-6) in modulating the epigenetic parameters in placenta and fetal liver.