| Intrauterine growth retardation (IUGR) has severe impacts on the growth and health of offspring, which causes great economic losses. Therefore, it will make great sense to improve and promote the growth and development of IUGR organism by nutritional intervention. Increasing evidence has shown that folic acid plays important roles in protein and nucleic acid synthesis, antioxidation and one-carbon unit metabolism. Maternal diet supplemented with folic acid ameliorated the bad effects of IUGR on newborn piglet to some extent, but there was no report about the effect of dietary folic acid addition in early postnatal on IUGR piglets. In the present study, we examined the effects of dietary folic acid levels on growth performance, hepatic structure and function of early postnatal IUGR piglets, and investigated the underlying mechanisms.A total of24crossbred (Duroc×Landrace×Yorkshire, DLY) male IUGR piglets (birth weight0.96±0.12kg, weaned weight2.74±0.32kg) and16DLY male NBW (normal birth weight) piglets (birth weight1.44±0.04kg, weaned weight4.54±0.40kg) weaned at14d of age were used in a21-d experiment. There were five experimental treatments, espacially the2X2factorial arrangement with the main effects of piglets (IUGR vs. NBW) and dietary addition of folic acid (0vs.5mg/kg); furthermore, another group of IUGR piglets fed basal diet with10mg/kg folic acid. The experiment included8replicate pens per treatment and1piglet per pen. At the end of the trial, intravenous blood and liver samples were collected. Serum sample was used to analyze serum folic acid (FA), homocysteine (Hey), methionine (Met), total protein (TP) and urea nitrogen (SUN) content as well as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Additionally, liver sample was weighed and used for assaying TP content, hepatocyte and hepatic lobule diameter, mRNA abundance of insulin like growth factor l(IGF-l), B-cell lymphoma-2(Bcl-2), bcl-2associated X protein (Bax), p53, cysteine-containing aspartate-specific proteases3(Caspase3), mammalian target of rapamycin (m-TOR), ubiquitin B (UbB), DNA methyltransferase1(DNMT-1), betaine homocysteine methyltransferase (BHMT) and methylene tetrahydrofolate reductase (MTHFR) as well as promoter methylation of p53.(1) IUGR piglets had a significantly lower body weight (P＜0.0001), ADG (P=0.02) and ADFI (P=0.003), and a higher feed utilization efficiency (P=0.05) than NBW piglets. Addition of5mg/kg folic acid had no effect on body weight and ADG of piglets (P>0.05), however, it caused lower ADFI (P=0.05) and F/G (P=0.05). Compared with IUGR+basal diet group, supplemented with10mg/kg folic acid significantly reduced ADG (P＜0.01).(2) Serum level of FA was lower in IUGR than in NBW piglets (P=0.02), while serum level of Met was higher in IUGR piglet (P=0.002). Supplementation with5mg/kg folic acid enhanced serum FA content (P＜0.0001) and decreased serum Hey (P=0.02) and Met levels (P=0.01), especially for the Met concentration in IUGR piglets. Compared to IUGR+5mg/kg folic acid group,10mg/kg folic acid further improved serum FA (P＜0.01) and had no significant effect on serum Hcy and Met contents (P>0.05).(3) IUGR piglets had lower serum TP content (P=0.04) and AST activity (P=0.002), as well as ALT activity (P=0.07). There was a piglet X diet interaction observed such that serum TP responses to the5mg/kg folic acid were higher in NBW piglets compared with IUGR piglets (P=0.003). Compared to IUGR+basal diet group, supplemented with10mg/kg folic acid significantly decreased serum TP content (P＜0.01) and elevated SUN level (P＜0.05) of IUGR piglets.(4) Liver weight was lower (P=0.001) and hepatic index (P=0.002) was higher in IUGR piglets. Hepatic TP content was fewer in IUGR groups (P=0.05), but it was tended to increase when5mg/kg folic acid was added (P=0.06), especially in NBW piglets. Hepatocyte diameter was greater in IUGR groups (P=0.003) and decreased by adding5mg/kg folic acid (P=0.01), especially for IUGR piglets. Compared with IUGR+basal diet group, supplemented with10mg/kg folic acid reduced hepatic TP content (P＜0.05), and had no effect on hepatic structure (P>0.05).(5) The pattern of promoter methylation of p53(P=0.07) and the transcript levels of hepatic IGF-1(P=0.07), Bcl-2(P=0.06), m-TOR (P=0.1) and DNMT-1(P=0.006) was lower in IUGR groups. However, p53(P=0.02), Bax (P=0.007) and UbB (P=0.01) transcript levels were increased in liver of IUGR piglets. Supplementation with5mg/kg folic acid, mRNA levels of p53(P=0.004) and Bax (P=0.02) showed decreased expression, in contrast, the pattern of promoter methylation of p53(P=0.008) and m-TOR mRNA (P=0.06) were up-regulated. Piglet X diet interaction on mRNA abundance of Bcl-2(P=0.04), p53(P=0.06), Bax (P=0.004), m-TOR (P=0.05) and UbB (P=0.07) was observed. Further, there was no difference in hepatic cell cycle, protein synthesis and degration between the IUGR+basal diet group and IUGR+10mg/kg folic aicd group (P>0.05).Together, the results suggest that IUGR piglets suffered impaired hepatic one-carbon unit metabolism, hepatic structure and protein metabolism and retarded growth performance. Diet supplemented with5mg/kg folic acid promoted feed utilization, ameliorated hepatic protein degradation and impaired structure in early-weaning IUGR piglets. However, supplementation with10mg/kg folic acid reduced growth performance and could not ameliorate the impaired hepatic structure and metabolic function in early-weaning IUGR piglets. The optimal dietary folic acid level of IUGR piglets needs further research. |
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