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Title: Enteral leucine supplementation increases protein synthesis in skeletal and cardiac muscles and visceral tissues of neonatal pigs through mTORC1-dependent pathways

Author
item SURYAWAN, AGUS - Children'S Nutrition Research Center (CNRC)
item TORRAZZA, ROBERTO - Children'S Nutrition Research Center (CNRC)
item GAZZANEO, MARIA - Children'S Nutrition Research Center (CNRC)
item ORELLANA, RENAN - Children'S Nutrition Research Center (CNRC)
item FIOROTTO, MARTA - Children'S Nutrition Research Center (CNRC)
item EL-KADI, SAMER - Children'S Nutrition Research Center (CNRC)
item SRIVASTAVA, NEERAJ - Children'S Nutrition Research Center (CNRC)
item NGUYEN, HANH - Children'S Nutrition Research Center (CNRC)
item DAVIS, TERESA - Children'S Nutrition Research Center (CNRC)

Submitted to: Pediatric Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/15/2012
Publication Date: 4/8/2013
Citation: Suryawan, A., Torrazza, R.M., Gazzaneo, M.C., Orellana, R.A., Fiorotto, M.L., El-Kadi, S.W., Srivastava, N., Nguyen, H.V., Davis, T.A. 2013. Enteral leucine supplementation increases protein synthesis in skeletal and cardiac muscles and visceral tissues of neonatal pigs through mTORC1-dependent pathways. Pediatric Research. 71(4.1):324-321.

Interpretive Summary: Studies show that an amino acid called leucine can stimulate the making of protein by the body. This effect of leucine is due to its ability to increase the activation of the protein-making machineries led by mTORC1. In our study, we used piglets to determine whether the addition ofleucine to their diets that have low protein content will enhance protein making in various tissues. Our results showed that leucine stimulated protein making by activating mTORC1. These findings are important because it suggests that leucine can be used as a potential ingredient to increase protein synthesis in the newborn children.

Technical Abstract: Leucine activates mammalian target of rapamycin (mTOR) to upregulate protein synthesis (PS). To examine enteral Leu effects on PS and signaling activation, 5-d-old piglets were fed for 24 h diets containing: (i) LP, (ii) LP+L, or (iii) HP. PS in skeletal muscles, heart, liver, pancreas, and jejunum, but not kidney, were greater in low protein supplemented with Leu (LP+L) than LP, but lower than high protein (HP). In longissimus dorsi muscle, protein kinase B phosphorylation was similar in LP and LP+L, but lower than HP. Although less than HP, p70 ribosomal S6 kinase 1 (S6K1) and eukaryotic initiation factor (eIF) 4E binding protein 1 (4EBP1) association with regulatory associated protein of mammalian target of rapamycin was greater in LP+L than LP, resulting in higher S6K1 and 4EBP1 phosphorylation. Feeding LP+L vs. LP decreased 4EBP1/eIF4E and increased eIF4E/eIF4G formation, but not to HP. Similar results were obtained for S6K1 and 4EBP1 phosphorylation in gastrocnemius, masseter, heart, liver, pancreas, and jejunum, but not kidney. eIF2a and elongation factor 2 phosphorylation was unaffected by treatment. Our results suggest that enteral Leu supplementation of a low protein diet enhances PS in most tissues through mTOR complex 1 pathways.