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

Abstract

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.

Leucine (and lysine) increased plasma levels of the satiety hormone cholecystokinin (CCK), and phenylalanine of the incretin glucagon-like peptide 1 (GLP-1) after oral gavages in pigs

“…In the present study Leu increased plasma levels of CCK but not of GLP-1, indicating a potentially stronger response from the proximal (where CCK is mainly produced by I cells of the enteroendocrine system) than the distal (the main site of production of GLP-1 by L-cells) small intestine ( Tian et al, 2019 ). Leu showed a less sustained effect on CCK secretion suggesting that the long-term impact on appetite may be partially explained by the release of other gut peptides or post absorptive signals associated with blood branched-chain AA (BCAA) imbalances interacting with the CNS ( Lynch et al, 2006 ; Kwon et al, 2019 ; Zhang et al, 2019 ).…”

An oral gavage of lysine elicited early satiation while gavages of lysine, leucine, or isoleucine prolonged satiety in pigs

“…High dietary levels of Leu and Ile showed a strong anorexigenic effect potentially mediated by CCK and GLP-1 in pigs ( Millet et al, 2015 ; Kwon et al, 2019 ; Tian et al, 2019a ; Müller et al, 2022 ). The activation of long-term satiety signals such as leptin and insulin have also been described associated to dietary BCAA in pigs ( Lynch et al, 2006 ; Zhang et al, 2019 ). Gut hormones have been involved in satiety resulting in an increase in the intermeal interval, which may explain the decreased feed intake in the Leu and Ile-gavaged pigs ( Overduin et al, 2014 ; Williams et al, 2016 ).…”

l-Leucine supplementation reduces growth performance accompanied by changed profiles of plasma amino acids and expression of jejunal amino acid transporters in breast-fed intra-uterine growth-retarded piglets

“…Unexpectedly, contrary to the growth promotion effect of leucine on normal suckling piglets, administration of leucine led to decreased production performance in IUGR piglets during suckling period, accompanied by lower plasma amino acid levels, changes in plasma biochemical parameters and the expression of amino acid transporters in the jejunum. Previous studies on weaned IUGR piglets (14–35 d of age) fed a basal diet supplemented with 0·3–0·35 % l -leucine have shown that l -leucine improves growth performance and glycolipid metabolism (32,43) . These evidence suggests that l -leucine is beneficial to IUGR piglets in response to weaning stress.…”