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Title: Leucine supplementation of an infant formula increases skeletal muscle and visceral tissue protein synthesis in a neonatal animal model 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 NGUYEN, HANH - Children'S Nutrition Research Center (CNRC)
item DAVIS, TERESA - Children'S Nutrition Research Center (CNRC)

Submitted to: Pediatric Academic Society
Publication Type: Abstract Only
Publication Acceptance Date: 11/18/2009
Publication Date: 5/1/2010
Citation: Murgas-Torrazza, R., Suryawan, A., Gazzaneo, M.C., Orellana, R.A., Nguyen, H.V., Davis, T.A. 2010. Leucine supplementation of an infant formula increases skeletal muscle and visceral tissue protein synthesis in a neonatal animal model by stimulating mTOR-dependent translation initiation [abstract]. In: Proceedings of the 2010 Pediatric Academic Societies Annual Conference, May 1-4, 2010, Vancouver, British Columbia, Canada. Paper No. 2750.10.

Interpretive Summary:

Technical Abstract: Low birth weight infants are often discharged weighing less than the tenth percentile for age and some remain small to adulthood with adverse long-term outcomes related to inadequate nutrition. Infant formula fortifiers had been used to improve the nutritional value of milk formulas. Leucine (Leu) appears to be the most effective single amino acid to trigger the activation of translation initiation factors that regulate protein synthesis in skeletal muscle but the effects of Leu in visceral tissues are not well understood. We hypothesized that enteral Leu supplementation of an infant formula in neonatal pigs will acutely increase skeletal muscle and visceral tissue protein synthesis to a rate similar to that achieved by feeding a high protein infant formula (HIF) and this stimulation will be greater than the one achieved by feeding infant formula alone (IF). Fasted 5-d-old piglets (n=6-7 per group) were gavage fed at 0 and 60 min either: 1) IF diet, 2) Infant formula supplemented with leucine (IF+L) to equal the Leu content in a HIF diet, or 3) HIF diet. Diets were isocaloric and lactose was equal. Protein content fed was the equivalent to a human protein intake of 1.5 g/kg(-1)/d(-1) in IF and IF+L, and of 7.65 g/kg(-1)/d(-1) in HIF. Fractional protein synthesis rates and translational control mechanisms were examined 90 min after feeding. Protein synthesis increased in longissimus dorsi, gastrocnemius, masseter, heart, jejunum, kidney and pancreas, but not liver, of the IF+L group compared to IF group alone and did not differ from HIF group. IF+L and HIF increased translational efficiency and phosphorylation of S6K1 and 4E-BP1 in all tissues except liver. In conclusion, our results suggest that an infant formula supplemented with leucine stimulates protein synthesis in skeletal muscle and most visceral tissues to a rate similar to that achieved by feeding high protein infant formulas and this stimulation involves activation of mTOR downstream effectors.