Dietary Leucine Supplementation Restores Serum Glucose Levels, and Modifying Hepatic Gene Expression Related to the Insulin Signal Pathway in IUGR Piglets

SIMPLE SUMMARY: Intrauterine malnutrition may compromise the size and structure of fetal organs and tissues, which leads to lower birth weight and a slower rate of growth after weaning. Intrauterine growth restriction/retardation (IUGR) impairs pancreas function, resulting in the decreased glucose levels in serum. Leucine, one of branched chain amino acids, is an essential amino acid and the substrate of protein synthesis. Leucine also acts as a major regulator of hormone signal transduction, like insulin. Dietary branched chain amino acids or leucine have beneficial effects on the glucose metabolism and glycogen synthesis of muscle. Leucine supplementation improves the insulin sensitivity in liver and muscle and then influences the systemic glucose homeostasis. However, it is still unclear whether leucine supplementation would alter insulin sensitivity in IUGR neonatal piglets. Our results showed that dietary leucine supplementation restored serum glucose concentrations, increased insulin and creatinine concentrations, and enhanced protein kinase adenosine monophosphate-activated γ 3-subunit and glucose transporter type 2 expression. These findings suggest that leucine might play a positive role in hepatic lipid metabolism and glucose metabolism in IUGR. ABSTRACT: This study aimed to investigate the effects of leucine with different levels on the insulin resistance in intrauterine growth restriction/retardation (IUGR) piglets. Thirty-two weaned piglets were arranged in a 2 × 2 factorial design and four treatments (n = 8) were as follow: (1) normal weaned piglets fed a basal diet (CONT), (2) IUGR weaned piglets fed a basal diet (IUGR), (3) normal weaned piglets fed a basal diet with the addition of 0.35% l-leucine (C-LEU), and (4) IUGR fed a basal diet with the addition of 0.35% l-leucine (I-LEU) for a 21-days trial. The results showed that compared to the IUGR group, the I-LEU group had higher final body weight and body weight gain, higher serum glucose concentrations, and higher serum insulin concentrations (p < 0.05). The gene expression of phosphatidylinositol 3-kinase p110 gamma, protein kinase adenosine monophosphate-activated γ 3-subunit, glycogen synthase kinase-3 alpha, and glucose transporter type 2 were increased in the I-LEU group as compared to the IUGR group (p < 0.05). It was concluded that dietary leucine supplementation restored serum glucose concentrations, increased insulin and creatinine concentrations, and enhanced protein kinase adenosine monophosphate-activated γ 3-subunit and glucose transporter type 2 expression, suggesting that leucine might play a positive role in hepatic lipid metabolism and glucose metabolism in IUGR.