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

Abstract

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.

The Impact of Nutrition and Environmental Epigenetics on Human Health and Disease

“…One study [ 45 ] demonstrated a strong association between whole peripheral blood DNA methylation and EPA and AA in two distinct human cohorts—lactating infants and adult men—of different ages and developmental stages, thereby linking EPA and AA to DNA hypermethylation. Another study [ 46 ] reported that maternal dyslipidemia caused significant epigenetic changes in placentas and fetal livers and also increased fetal liver triacylglycerol accumulation. It has been shown from animal experiments that cardiovascular and metabolic diseases, particularly in males, may develop from alterations in DNA methylation.…”

Being Born Large for Gestational Age is Associated with Increased Global Placental DNA Methylation

“…Interestingly, an intervention with dietary n-3 fatty acids reversed these alterations 68 . Current literature suggests that the link between dietary lipids and DNA methylation might be due to their involvement in one carbon metabolism 68,69 . Thus, the maternal genetic setup or consumed diet 70 , key factors that affect blood lipid profiles, might also impact on placental lipid metabolism and DNA methylation during pregnancy.…”

“…Global DNA methylation has been reported to be associated with lipid metabolism and plasma glucose concentration 67 . It was demonstrated in a rat model that maternal dyslipidemia, induced by feeding a high fat diet, increases global placental DNA methylation 68 . Interestingly, an intervention with dietary n-3 fatty acids reversed these alterations 68 .…”

“…It was demonstrated in a rat model that maternal dyslipidemia, induced by feeding a high fat diet, increases global placental DNA methylation 68 . Interestingly, an intervention with dietary n-3 fatty acids reversed these alterations 68 . Current literature suggests that the link between dietary lipids and DNA methylation might be due to their involvement in one carbon metabolism 68,69 .…”

The Role of Nutri(epi)genomics in Achieving the Body’s Full Potential in Physical Activity

“…In the Western diet, for example, saturated fats, red meats, and refined carbohydrates tend to exceed fresh fruits and vegetables, whole grains, seafood, and poultry. Not surprisingly, this dietary regimen has been linked to hypertension, heart disease, diabetes and increased risk of cancer, outcomes that likely occur via epigenetic alterations [ 281 , 282 , 283 , 284 ]. By contrast, the Mediterranean diet, which is traditionally rich in fruits, vegetables, fish and poultry, whole grains and healthy fats (monounsaturated and polyunsaturated fats), but poor in red meat and saturated fats, is associated with a reduced risk of overall mortality [ 285 , 286 ].…”