Dietary arginine supplementation increases mTOR signaling activity in skeletal muscle of neonatal pigs.
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Dietary arginine supplementation increases growth of neonatal pigs, but the underlying mechanisms are unknown. This study was conducted to test the hypothesis that the arginine treatment activates translation initiation factors and protein synthesis in skeletal muscle. Piglets were fed milk-based diets supplemented with 0 or 0.6% L-arginine between 7 and 14 d of age. Following a 7-d period of arginine supplementation, at 1 h after the last meal, jugular venous blood samples were obtained for metabolite analysis, whereas longissimus muscle and liver were collected to determine the abundance and phosphorylation state of the mammalian target of the rapamycin (mTOR), ribosomal protein S6 kinase 1 (S6K1), eukaryotic initiation factor (eIF) 4E-binding protein-1 (4E-BP1), eIF4E, and eIF4G. Fractional rates of protein synthesis were measured in muscle and liver using the [(3)H]phenylalanine flooding-dose technique. Arginine supplementation increased (P < 0.05) daily gain, the plasma insulin concentration, and protein synthesis in skeletal muscle but not in liver. The arginine treatment enhanced the formation of the active eIF4E x eIF4G complex but reduced the amount of the inactive 4E-BP1 x eIF4E complex in muscle. These changes were associated with elevated levels of phosphorylated mTOR and 4E-BP1 in muscle of arginine-supplemented piglets (P < 0.05). Neither the total amounts nor phosphorylation levels of the translation initiation factors in the liver differed between control and arginine-supplemented piglets. Collectively, these results suggest that dietary arginine supplementation increases mTOR signaling activity in skeletal muscle, but not in liver, of milk-fed neonatal pigs. The findings provide a molecular mechanism for explaining the previous observation that increased circulating arginine stimulated muscle protein synthesis and promoted weight gain in neonatal pigs.