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.