title: Physiological rise in plasma leucine stimulates muscle protein synthesis in neonatal pigs by enhancing translation initiation factor activation.
abstract: Protein synthesis in skeletal muscle of adult rats increases in response to oral gavage of supraphysiological doses of leucine. However, the effect on protein synthesis of a physiological rise in plasma leucine has not been investigated in neonates, an anabolic population highly sensitive to amino acids and insulin. Therefore, in the current study, fasted pigs were infused intra-arterially with leucine (0, 200, or 400 micromol.kg(-1).h(-1)), and protein synthesis was measured after 60 or 120 min. Protein synthesis was increased in muscle, but not in liver, at 60 min. At 120 min, however, protein synthesis returned to baseline levels in muscle but was reduced below baseline values in liver. The increase in protein synthesis in muscle was associated with increased plasma leucine of 1.5- to 3-fold and no change in plasma insulin. Leucine infusion for 120 min reduced plasma essential amino acid levels. Phosphorylation of eukaryotic initiation factor (eIF)-4E-binding protein-1 (4E-BP1), ribosomal protein (rp) S6 kinase, and rpS6 was increased, and the amount of eIF4E associated with its repressor 4E-BP1 was reduced after 60 and 120 min of leucine infusion. No change in these biomarkers of mRNA translation was observed in liver. Thus a physiological increase in plasma leucine stimulates protein synthesis in skeletal muscle of neonatal pigs in association with increased eIF4E availability for eIF4F assembly. This response appears to be insulin independent, substrate dependent, and tissue specific. The results suggest that the branched-chain amino acid leucine can act as a nutrient signal to stimulate protein synthesis in skeletal muscle of neonates.
authors.affiliation: United States Department of Agriculture/Agricultural Research Service, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, 1100 Bates St., Suite 9064, Houston, TX 77030, USA.
authors.forename: Jeffery
authors.initials: J
authors.lastname: Escobar
authors.forename: Jason W
authors.initials: JW
authors.lastname: Frank
authors.forename: Agus
authors.initials: A
authors.lastname: Suryawan
authors.forename: Hanh V
authors.initials: HV
authors.lastname: Nguyen
authors.forename: Scot R
authors.initials: SR
authors.lastname: Kimball
authors.forename: Leonard S
authors.initials: LS
authors.lastname: Jefferson
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Davis
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D039642:Eukaryotic Initiation Factors / Q000378:metabolism*; D007261:Infusions, Intra-Arterial; D007930:Leucine / Q000008:administration & dosage / Q000097:blood*; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000502:physiology*; D013552:Swine
chemical_list: D039642:Eukaryotic Initiation Factors; D009124:Muscle Proteins; D007930:Leucine