Title: INFUSION OF A PHYSIOLOGICAL DOSE OF LEUCINE STIMULATES MUSCLE PROTEIN SYNTHESIS IN NEONATAL PIGS BY ENHANCING THE ACTIVITY OF TRANSLATION INITIATION FACTORS Authors
|Escobar, Jeffery - BAYLOR COLL OF MEDICINE|
|Frank, Jason - BAYLOR COLL OF MEDICINE|
|Kimball, Scot - UNIV OF PENN COL OF MED|
|Nguyen, Hanh - BAYLOR COLL OF MEDICINE|
|Liu, Chun - BAYLOR COLL OF MEDICINE|
|Jefferson, Leonard - UNIV OF PENN COL OF MED|
Submitted to: Journal of Animal Science Supplement
Publication Type: Abstract Only
Publication Acceptance Date: April 1, 2004
Publication Date: July 25, 2004
Citation: Escobar, J., Frank, J.W., Kimball, S.R., Suryawan, A., Nguyen, H.V., Liu, C.W., Jefferson, L.S., Davis, T.A. 2004. Infusion of a physiological dose of leucine stimulates muscle protein synthesis in neonatal pigs by enhancing the activity of translation initiation factors [abstract]. Journal of Animal Science, Proceedings of the 2004 Joint Annual Meeting of the American Society of Animal Science. 82(Suppl. 1):abstract 767, p. 419. Interpretive Summary: Not required for an abstract.
Technical Abstract: In adult rats, skeletal muscle protein synthesis increases in response to pharmacological doses of leucine (Leu) administered orally. The effect of a physiological rise in plasma Leu on skeletal muscle protein synthesis has not been investigated in neonatal pigs, which are highly sensitive to amino acid and insulin stimulation. Thus, 24 crossbred pigs were food-deprived for 12 h and intra-arterially infused with Leu (0 or 400 mmolkg[-1]h[-1]). Protein synthesis was measured after 60 or 120 min in liver, and longissimus dorsi and gastrocnemius muscles. Infusion of Leu increased (P < 0.01) plasma Leu 2.5- to 3.4-fold while plasma insulin and glucose were unchanged. Infusing Leu for 120 min, but not for 60 min, reduced (P < 0.05) plasma essential amino acids levels. Infusing Leu for 60 and 120 min increased (P < 0.05) phosphorylation of eukaryotic initiation factor (eIF) 4E binding protein-1 (4E-BP1), ribosomal protein (rp) S6 kinase (S6K1), and rpS6, and decreased the amount of eIF4E associated with its repressor, 4E-BP1, in longissimus dorsi muscle. In liver, phosphorylation of 4E-BP1, S6K1 and rpS6, as well as eIF4E associated with 4E-BP1 were not affected by Leu infusion. Leucine infusion for 60 min increased protein synthesis in longissimus dorsi (38%, P = 0.04) and gastrocnemius (67%, P = 0.005) muscles, but not in liver (P = 0.11). Leucine infusion for 120 min did not increase protein synthesis in skeletal muscle and reduced protein synthesis in liver (25%, P < 0.01). Thus, a physiological increase in plasma Leu stimulates protein synthesis in skeletal muscle of neonatal pigs by increasing eIF4E availability for eIF4F assembly. Moreover, this response appears to be insulin-independent, substrate-dependent, and tissue-specific.