5-Methyltetrahydrofolate in Maternal Diets Alters DNA Methylation Potential and Increases Later Life Weight Gain and Food Intake in Wistar Rat Dams and Female Offspring (P11-022-19)

Abstract Objectives Diet during pregnancy programs the mother and offspring post-weaning (PW). Folic acid (FA, synthetic folate) mediates DNA methylation (DNAm) reactions and high intakes, simulating those consumed by American women, lead to epigenetic dysregulation of energy metabolic pathways. 5-methyltetrahydrofolate (5MTHF), the bioactive folate form, has gained popularity as a supplement due to direct cellular uptake and utilization and does not increase unmetabolized FA (UMFA). However, a comparison of folate forms on in utero programming of offspring or maternal health has not been reported. Our objectives were to compare the effects of folate dose (low vs high) and form (FA vs 5MTHF) during pregnancy on DNAm potential, and the early and later PW phenotype of Wistar rat mothers and female offspring (mothers-to-be). Methods Pregnant Wistar rats (n = 22/group) were fed an AIN93G diet with recommended FA (1X, 2mg/kg diet), 5X-FA or equimolar 5MTHF. Dams were fed 1X-FA during lactation and then dams and female pups were fed a high fat diet for 19 weeks. Weight gain (WG), food intake (FI), energy expenditure (EE), insulin resistance (IR), plasma 5MTHF, UMFA, homocysteine (tHcy), and hepatic S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) and DNA methyltransferases (DNMT) activity at birth and PW were measured. Results Dams fed 5M...