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Title: Leucine supplementation of a low-protein meal increases skeletal muscle and visceral tissue protein synthesis in neonatal pigs by stimulating mTOR-dependent translation initiation

Author
item MURGAS-TORRAZZA, ROBERTO - 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 FRANK, JASON - University Of Arkansas
item NGUYEN, HANH - 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 DAVIS, TERESA - Children'S Nutrition Research Center (CNRC)

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/12/2010
Publication Date: 10/20/2010
Citation: Murgas-Torrazza, R., Suryawan, A., Gazzaneo, M.C., Orellana, R.A., Frank, J.W., Nguyen, H.V., Fiorotto, M.L., El-Kadi, S.W., Davis, T.A. 2010. Leucine supplementation of a low-protein meal increases skeletal muscle and visceral tissue protein synthesis in neonatal pigs by stimulating mTOR-dependent translation initiation. Journal of Nutrition. 140(12):2145-2152.

Interpretive Summary: In our previous research, we demonstrated that infusion of leucine via intravenous infusion stimulates skeletal muscle protein synthesis through the activation of signaling components. In this study, we examined the effect of leucine supplementation of a low protein diet on protein synthesis and the activation of signaling components in neonatal pigs. We found that leucine supplementation increased protein synthesis in skeletal muscle and in most of visceral tissues to the rate achieved by a high-protein diet. The results suggest that leucine supplementation has the potential to be an adjunct in the nutritional management of infants as it may enhance growth.

Technical Abstract: Protein synthesis and eukaryotic initiation factor (eIF) activation are increased in skeletal muscle of neonatal pigs parenterally infused with amino acids. Leucine appears to be the most effective single amino acid to trigger these effects. To examine the response to enteral leucine supplementation, overnight food-deprived 5-d-old pigs were gavage fed at 0 and 60 min a: "1") low-protein diet (LP); "2") LP supplemented with leucine (LP+L) to equal leucine in the high-protein diet (HP); or "3") HP diet. Diets were isocaloric and equal in lactose. Fractional protein synthesis rates and translation initiation control mechanisms were examined in skeletal muscles and visceral tissues 90 min after feeding. Protein synthesis rates in longissimus dorsi, gastrocnemius, and masseter muscles, heart, jejunum, kidney, and pancreas, but not liver, were greater in the LP+L group compared with the LP group and did not differ from the HP group. Feeding LP+L and HP diets compared with the LP diet increased phosphorylation of mammalian target of rapamycin (mTOR), 4E-binding protein 1, ribosomal protein S6 kinase-1, and eIF4G and formation of the active eIF4E/eIF4G complex in longissimus dorsi muscle. In all tissues except liver, activation of mTOR effectors increased in pigs fed LP+L and HP vs. LP diets. Our results suggest that leucine supplementation of a low-protein meal stimulates protein synthesis in muscle and most visceral tissues to a rate similar to that achieved by feeding a high-protein meal and this stimulation involves activation of mTOR downstream effectors.