Effect of folic acid supplementation on hepatic antioxidant function and mitochondrial-related gene expression in weanling intrauterine growth retarded piglets

Abstract

The aim of the present study was to investigate the effect of dietary folic acid supplementation on antioxidant function and mRNA expression levels of genes involved in mitochondrial biogenesis and function in the liver of piglets affected by intrauterine growth retardation (IUGR). Sixteen piglets at normal birth weight and 16 IUGR piglets were fed either a control diet (C) or a folic acid-supplemented diet (FS, C+5mg/kg folic acid) from 14d of age to 35d of age postnatal. Blood and liver samples were collected at the end of the study. The results showed that body weight was lower for IUGR piglets than that of NBW piglets at 14d of age and 35d of age postnatal (P<0.05). Dietary folic acid supplementation increased plasma folic acid concentrations and hepatic GPx activity, but decreased plasma homocysteine levels (P<0.05). Reduced activities of Mn-SOD and T-AOC, mitochondrial DNA (mtDNA) content, and ATP concentration (P<0.05) were observed in the liver of IUGR pigs fed a control diet. However, the changes in mtDNA content and activities of Mn-SOD and T-AOC were negated in IUGR pigs fed a FS diet (P<0.05). Also, dietary folic acid supplementation decreased protein carbonyls and MDA concentration in the liver of IUGR piglets (P<0.05). Expression levels of genes encoding for PPARγ coactivator-1α (PGC-1α), mammalian silencing information regulator-2α (SIRT-1), nuclear respiratory factor-1 (NRF-1), mt transcription factor A (TFAM), mt single-strand DNA-binding protein (mt SSB), mt polymerase r (mt polr), glucokinase, citrate synthase (CS), ATP synthase (ATPS), and cytochrome c oxidase (CcOX) subunit I and V were decreased in IUGR piglets compared with NBW piglets. However, mRNA levels of PGC-1α, SIRT-1, NRF-1, TFAM, and mt polr in the liver of IUGR pigs fed FS diet were not different from that of NBW pigs. Gene mRNA expression abundance of CcOX IV was enhanced by folic acid supplementation (P<0.05) regardless of birth weight. The present study indicates that IUGR impaired hepatic antioxidant function and mRNA expression levels of genes are involved in mitochondrial biogenesis and function. Dietary folic acid supplementation prevented the harmful effect of IUGR on hepatic antioxidant function and mtDNA biogenesis, but had no effect on mRNA expression levels of genes involved in mitochondrial function.