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

Xue Yang,Yifan Huang,Changhao Sun,Jie Li

doi:10.3390/nu9090935

Abstract

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.

Highlights

Increasing evidence demonstrates that the risk of metabolic diseases in adulthood is determined by diet and lifestyle in adulthood, and the environmental [1], especially nutritional, exposure in early life [2,3,4]
Our findings demonstrate that maternal prenatal folic acid supplementation (FAS) leads to elevated serum and liver TG
Maternal prenatal FAS induced persistently decreased expression of hepatic Adipose triglyceride lipase (ATGL) and and adipose Lipoprotein lipase (LPL), which was potentially caused by elevated DNA methylation levels within ATGL

Summary

Introduction

Increasing evidence demonstrates that the risk of metabolic diseases in adulthood is determined by diet and lifestyle in adulthood, and the environmental [1], especially nutritional, exposure in early life [2,3,4]. The effects of in utero and early-life nutritional exposure on adult metabolic diseases are thought to be mediated, at least in part, by epigenetic processes [1]. Maternal methyl donor supplementation before and during pregnancy has been found to permanently affect the DNA methylation at some genomic loci in the offspring, resulting in persistent phenotypic modification in offspring [8,9]. Whether maternal folate supplementation has the potential to alter DNA methylation modification of genes involved in glucose and lipid metabolism in embryo and fetus and program risk of metabolic diseases in adult offspring is still unclear

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