Leucine Supplementation of a Protein and Energy Restricted Diet Enhances mTORC1 Activation but not Protein Synthesis in Muscle of Neonatal Pigs

Low birth weight infants can experience insufficient protein accretion due to feeding intolerance or poor amino acid (AA) and energy absorption during the shift from parenteral to oral feeding. The objective of this study was to test if enteral leucine (Leu) supplementation can increase protein synthesis in skeletal muscle of neonates who consume 30% less crude protein (CP) and metabolic energy (ME) than their requirements, and whether the changes are mediated through the mammalian target of rapamycin complex 1 (mTORC1) pathway. Four‐day‐old piglets were fed by gastric tube 1 of 3 diets containing (kg BW/d) 16 g CP and 190 kcal ME (CON), 10.9 g CP and 132 kcal ME (R), or 10.8 g CP + 0.2 % Leu and 136 kcal ME (RL) at 4‐h intervals for 8 d. On d 8, plasma AA and insulin levels were measured at 30, 60, 90, 120, 180 and 240 min post‐feeding. Protein synthesis rates (KS) and mTORC1 activation were examined 120 min post‐feeding. At 120 min Leu was higher in RL, and insulin, isoleucine and valine were higher in CON. Compared to RL and R, the CON diet increased body weight, KS, activation of S6 kinase (pS6K1), 4E‐binding protein (p4EBP1) and eukaryotic initiation factor 4 complex (eIF4E·eIF4G). RL increased pS6K1, p4EBP1 and eIF4E·eIF4G compared to R. In conclusion, Leu inclusion in a CP and ME‐restricted diet does not improve body weight or protein synthesis, but increases mTORC1 activation in skeletal muscle of piglets. The reduced protein and energy supply may limit the ability of leucine to enhance muscle protein accretion in neonates. NIH AR444474, NIH HD072891, USDA NIFA 2013‐67015‐20438, and USDA/ARS 6250‐51000‐055