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Title: Leucine supplementation of a chronically restricted protein and energy diet enhances mTOR pathway activation but not muscle protein synthesis in neonatal pigs

Author
item MARJARIN, RODRIGO - Children'S Nutrition Research Center (CNRC)
item COLUMBUS, DANIEL - Children'S Nutrition Research Center (CNRC)
item SURYAWAN, AGUS - Children'S Nutrition Research Center (CNRC)
item HERNANDEZ-GARCIA, ADRIANA - Children'S Nutrition Research Center (CNRC)
item HOANG, NGUYET-MINH - Children'S Nutrition Research Center (CNRC)
item FIOROTTO, MARTA - Children'S Nutrition Research Center (CNRC)
item DAVIS, TERESA - Children'S Nutrition Research Center (CNRC)

Submitted to: Amino Acids
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/15/2015
Publication Date: 9/3/2015
Citation: Marjarin, R., Columbus, D.A., Suryawan, A., Hernandez-Garcia, A.D., Hoang, N., Fiorotto, M.L., Davis, T.A. 2015. Leucine supplementation of a chronically restricted protein and energy diet enhances mTOR pathway activation but not muscle protein synthesis in neonatal pigs. Amino Acids. 48(1):257-267.

Interpretive Summary: Many low-birth-weight infants are fed less than their protein and energy requirement for growth due to feeding intolerance and concern for possible adverse events associated with the escalation of feed. Scientists at the Children's Nutrition Research Center in Houston, TX conducted studies in the neonatal piglet model to determine whether supplementation with the amino acid, leucine, can promote muscle growth in newborns even when they are consuming less than their energy and protein requirements. We showed that leucine supplementation stimulated the intracellular signaling pathways that regulate the synthesis of muscle protein. However, when energy and protein intakes were limited, provision of additional leucine was not able to further stimulate the synthesis of muscle protein or improve short-term growth. These studies emphasize the importance of provision of sufficient energy and protein to promote optimal growth of newborns.

Technical Abstract: Suboptimal nutrient intake represents a limiting factor for growth and long-term survival of low-birth weight infants. The objective of this study was to determine if in neonates who can consume only 70 % of their protein and energy requirements for 8 days, enteral leucine supplementation will upregulate the mammalian target of rapamycin (mTOR) pathway in skeletal muscle, leading to an increase in protein synthesis and muscle anabolism. Nineteen 4-day-old piglets were fed by gastric tube 1 of 3 diets, containing (kg body weight(-1)/day(-1)16 g protein and 190 kcal (CON), 10.9 g protein and 132 kcal (R), or 10.8 g protein + 0.2 % leucine and 136 kcal (RL) at 4-h intervals for 8 days. On day 8, plasma AA and insulin levels were measured during 6 post-feeding intervals, and muscle protein synthesis rate and mTOR signaling proteins were determined at 120 min post-feeding. At 120 min, leucine was highest in RL (P < 0.001), whereas insulin, isoleucine and valine were lower in RL and R compared to CON (P < 0.001). Compared to RL and R, the CON diet increased (P < 0.01) body weight, protein synthesis, phosphorylation of S6 kinase (p-S6K1) and 4E-binding protein (p-4EBP1), and activation of eukaryotic initiation factor 4 complex (eIF4E/eIF4G). RL increased (P = 0.01) p-S6K1, p-4EBP1 and eIF4E/eIF4G compared to R. In conclusion, when protein and energy intakes are restricted for 8 days, leucine supplementation increases muscle mTOR activation, but does not improve body weight gain or enhance skeletal muscle protein synthesis in neonatal pigs.