Leucine stimulation of skeletal muscle protein synthesis during prolonged leucine infusion is dependent on amino acid availability

Abstract

Leucine stimulates protein synthesis in cultured cells, mature rats and neonatal pigs. We have reported that leucine infusion increases protein synthesis in skeletal muscle of neonatal pigs during a 60-min infusion. When leucine infusion was prolonged for 120 min, however, protein synthesis was not increased. We hypothesized that this lack of responsiveness was due to a decrease (−50%) in plasma essential amino acids (AA). To test this hypothesis, fasted neonatal pigs were infused with leucine (0 or 400 μmol·kg−1·h−1) for 120 min to raise plasma leucine within the physiological postprandial range in the presence or absence of the infusion of an AA mixture (without leucine) to maintain plasma AA levels. Parenteral AA administration prevented the leucine induced reduction (P < 0.05) in plasma essential AA. Leucine infusion, regardless of AA treatment, increased (P < 0.05) the phosphorylation of eukaryotic initiation factor (eIF) 4E binding protein-1 (4E-BP1), decreased the inactive 4E BP1·eIF4E complex, and increased the active eIF4G·eIF4E complex in longissimus dorsi muscle. Protein synthesis was increased (P < 0.02, +54%) in muscle with infusion of both leucine and AA but not with leucine alone. In liver, neither protein synthesis nor activation of translation initiation factors was affected by leucine infusion with or without AA. Thus, the stimulation of protein synthesis during prolonged leucine infusion is tissue specific and dependent on AA availability (NIH AR 44474 and USDA 58-6250-6-001)