163. MATERNAL FOLIC ACID SUPPLEMENTATION INDUCED ALTERATIONS IN METABOLIC HEALTH OF PROGENY: ROLE OF microRNA REGULATORY NETWORKS

Abstract

Background: Nutrition in early life can influence metabolic functionality in later life, in part via heritable epigenetic changes, which modify gene expression without altering DNA sequence. Folate supplies methyl groups for the methylation of DNA and histones, both major epigenetic marks that change dynamically in utero. We have recently shown that maternal folic acid supplementation (MFAS) in the pregnant rat increases insulin sensitivity in adult male progeny, while decreasing that of females. The molecular basis of this is unknown but microRNAs may play a role. MicroRNAs are epigenetically regulated non-coding RNAs that downregulate post-transcriptional expression of their targets. MFAS may modulate epigenetics and expression of microRNAs and their targets in adult progeny to alter insulin sensitivity. Aims/Hypotheses: The effect of MFAS before and throughout pregnancy on microRNA expression in liver and skeletal muscle of adult progeny was determined. Methods: Female Wistar rats were fed Control (n=11) or Folic Acid Supplemented (n=9) diets containing either 2 or 6 mg folic acid/kg respectively, from two weeks before mating and throughout pregnancy. One male and female progeny per litter were sacrificed on postnatal day 90 and microRNA expression was determined by Exiqon microRNA microarray v.8.1. Results: MFAS altered hepatic microRNA expression in adult male progeny, but did not alter that in females. Sixteen hepatic microRNAs were differentially expressed, with five predicted in silico (rno-miR: 23a, 23b, 212, 298 and 325-5p) to target several key insulin signalling molecules (p85α, p110β, Akt2, and Prkcz). miR-122a, which promotes cholesterol and lipid synthesis in vivo, was also downregulated. MFAS did not alter microRNA expression in skeletal muscle of adult male or female progeny. Conclusions: MFAS alters hepatic microRNA expression in adult male progeny. Changes in their expression together with their targets in insulin signalling pathway may initiate increased insulin sensitivity in adult male progeny.