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Title: Stimulation of muscle protein synthesis by prolonged parenteral infusion of leucine is dependent on amino acid availability in neonatal pigs

Author
item WILSON, FIONA - Children'S Nutrition Research Center (CNRC)
item SURYAWAN, AGUS - 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 NGUYEN, HANH - Children'S Nutrition Research Center (CNRC)
item DAVIS, TERESA - Children'S Nutrition Research Center (CNRC)

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/16/2009
Publication Date: 12/23/2009
Citation: Wilson, F.A., Suryawan, A., Gazzaneo, M.C., Orellana, R.A., Nguyen, H.V., Davis, T.A. 2010. Stimulation of muscle protein synthesis by prolonged parenteral infusion of leucine is dependent on amino acid availability in neonatal pigs. Journal of Nutrition. 140(2):264-270.

Interpretive Summary: After feeding, the rise in amino acids especially leucine, can stimulate protein synthesis in newborn animals. In early studies, we showed that 1 hour infusion of leucine stimulate protein synthesis. However, 2 hour leucine infusion had no effect unless amino acids levels were prevented from falling. This study was conducted to see whether 24 hour leucine infusion would have a similar effect to these previous studies. The results show that as long as amino acid replacement is provided, 24 hour leucine infusion can stimulate protein synthesis. In summary, longer leucine, infusion is possible to induce protein synthesis in newborn pigs. The results of this study provide valuable information that can be used to design clinical feeding programs to help sick newborns. The public will benefit by understanding important aspects of human nutrition.

Technical Abstract: The postprandial rise in amino acids, particularly leucine, stimulates muscle protein synthesis in neonates. Previously, we showed that a 1-h infusion of leucine increased protein synthesis, but this response was not sustained for 2 h unless the leucine-induced decrease in amino acids was prevented. To determine whether a parenteral leucine infusion can stimulate protein synthesis for a more prolonged, clinically relevant period if baseline amino acid concentrations are maintained, overnight food-deprived neonatal pigs were infused for 24 h with saline, leucine (400 micromol/kg(–1)/h(–1)), or leucine with replacement amino acids. Amino acid replacement prevented the leucine-induced decrease in amino acids. Muscle protein synthesis was increased by leucine, but only when other amino acids were supplied to maintain euaminoacidemia. Leucine did not affect activators of mammalian target of rapamycin (mTOR), i.e. protein kinase B, AMP-activated protein kinase, tuberous sclerosis complex 2, or eukaryotic elongation factor 2. There was no effect of treatment on the association of mTOR with regulatory associated protein of mammalian target of rapamycin (raptor), G-protein beta subunit-like protein, or rictor or the phosphorylation of raptor or proline-rich Akt substrate of 40 kDa. Phosphorylation of mTOR and its downstream targets, eukaryotic initiation factor (eIF) 4E binding protein and ribosomal protein S6 kinase, and the eIF4E/eIF4G association were increased and eIF2alpha phosphorylation was reduced by leucine and was not further altered by correcting for the leucine-induced hypoaminoacidemia. Thus, prolonged parenteral infusion of leucine activates mTOR and its downstream targets in neonatal skeletal muscle, but the stimulation of protein synthesis also is dependent upon amino acid availability.