Location: Children's Nutrition Research CenterTitle: Differential effects of long-term leucine infusion on tissue protein synthesis in neonatal pigs Author
Submitted to: Amino Acids
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/11/2010
Publication Date: 5/27/2010
Citation: Wilson, F.A., Suryawan, A., Orellana, R.A., Gazzaneo, M.C., Nguyen, H.V., Davis, T.A. 2010. Differential effects of long-term leucine infusion on tissue protein synthesis in neonatal pigs. Amino Acids. 40(1):157-165. Interpretive Summary: Leucine is a unique amino acid which can promote protein synthesis by activating the intracellular signaling components that regulate translation. In a previous study, we found that acute infusion of leucine enhanced protein synthesis as long as all amino acids are maintained in proper levels. The current study was conducted to determine whether long term leucine infusion can stimulate protein synthesis. We found that leucine stimulates protein synthesis in skeletal muscle and visceral tissues. The effect of leucine on protein synthesis is due to leucine’s effect on the activation of signaling components responsible for the protein synthesis process. In summary, 24 hour leucine infusion can increase protein synthesis in tissues of neonatal pigs. This study is important because it shows that leucine may be beneficial to stimulate protein synthesis and growth of human neonates.
Technical Abstract: Leucine is unique among the amino acids in its ability to promote protein synthesis by activating translation initiation via the mammalian target of rapamycin (mTOR) pathway. Previously, we showed that leucine infusion acutely stimulates protein synthesis in fast-twitch glycolytic muscle of neonatal pigs but this response cannot be maintained unless the leucine-induced fall in amino acids is prevented. To determine whether leucine can stimulate protein synthesis in muscles of different fiber types and in visceral tissues of the neonate in the long-term if baseline amino acid concentrations are maintained, overnight fasted neonatal pigs were infused for 24 h with saline, leucine (400 micromol kg(-1) h(-1)), or leucine with replacement amino acids to prevent the leucine-induced hypoaminoacidemia. Changes in the fractional rate of protein synthesis and activation of mTOR, as determined by eukaryotic initiation factor 4E binding protein (4E-BP1) and S6 kinase 1 (S6K1) phosphorylation, in the gastrocnemius and masseter muscles, heart, liver, jejunum, kidney, and pancreas were measured. Leucine increased mTOR activation in the gastrocnemius and masseter muscles, liver, and pancreas, in both the absence and presence of amino acid replacement. However, protein synthesis in these tissues was increased only when amino acids were infused to maintain baseline levels. There were no changes in mTOR signaling or protein synthesis in the other tissues we examined. Thus, long-term infusion of leucine stimulates mTOR signaling in skeletal muscle and some visceral tissues but the leucine-induced stimulation of protein synthesis in these tissues requires sustained amino acid availability.