Maternal Prenatal Folic Acid Supplementation Programs Offspring Lipid Metabolism by Aberrant DNA Methylation in Hepatic ATGL and Adipose LPL in Rats

The effects of maternal prenatal folic acid supplementation (FAS) on offspring lipid metabolism in adulthood remains unclear, although prenatal FAS is compulsively suggested in many countries. Female Sprague-Dawley rats were fed with control (CON) or FAS diets before and during pregnancy. Male offspring of CON and FAS dams were further divided into two groups at seven weeks for CON and high-fat (HF) diet interventions for eight weeks in adulthood (n = 10). The interactive effects of maternal prenatal FAS and offspring HF in adulthood on lipid metabolism and DNA methylation of genes involved in lipids metabolism were assessed. The male offspring of FAS dams had elevated serum and liver triglyceride level when fed with HF compared to the male offspring of CON dams. The mRNA and protein expression levels of hepatic ATGL and adipose LPL were significantly decreased in offspring of FAS dams than in offspring of CON dams. Furthermore, maternal prenatal FAS resulted in elevated DNA methylation levels in the promoter and first exon region of hepatic ATGL and adipose LPL in offspring. Maternal FAS exacerbated the adverse effects of HF on lipid metabolism in offspring through inducing aberrant DNA methylation levels of hepatic ATGL and adipose LPL.