Long‐term leucine induced stimulation of muscle protein synthesis is amino acid dependent

Infusing leucine for 1 h increases skeletal muscle protein synthesis in the neonate, but this is not sustained for 2 h unless the corresponding fall in amino acids is prevented. This study aimed to determine whether a continuous leucine infusion can stimulate protein synthesis for a prolonged period when baseline amino acid concentrations are maintained. Overnight fasted neonatal pigs (n = 18) were infused for 24 h with saline, leucine (400 µmol · kg −1 · h −1 ),or leucine with replacement amino acids. Leucine stimulated muscle protein synthesis only when other amino acids were maintained at fasting. Leucine had no effect on the phosphorylation of protein kinase B, AMP‐activated protein kinase, tuberous sclerosis complex 2, or eukaryotic elongation factor 2, the association of mTOR with raptor, G‐protein ßsubunit‐like protein, or rictor, or the phosphorylation of raptor or proline‐rich Akt Substrate of 40 kDa. Phosphorylation of mTOR, eukaryotic initiation factor (eIF) 4E binding protein (4EBP1) and ribosomal protein S6 kinase, and eIF4E▸eIF4G association were increased and eIF2 phosphorylation was reduced by leucine, in the absence and presence of replacement amino acids. Thus, prolonged infusion of leucine activates mTOR and its downstream targets in skeletal muscle; however, protein synthesis stimulation is dependent upon amino acid availability. (Supported by Ajinomoto Amino Acid Research Program).