Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/12/2007
Publication Date: 9/18/2007
Publication URL: //ajpendo.physiology.org/cgi/reprint/293/6/E1615?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=1&author1=Escobar%2C+J&andorexacttitle=and&andorexacttitleabs=and&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT
Citation: Escobar, J., Frank, J.W., Suryawan, A., Nguyen, H.V., Davis, T.A. 2007. Amino acid availability and age affect the leucine stimulation of protein synthesis and eIF4F formation in muscle. American Journal of Physiology-Endocrinology and Metabolism. 293(6):E1615-E1621. Interpretive Summary: Growth is very rapid in the newborn because feeding stimulates the synthesis of proteins in all tissues of the body. This response to feeding is, in part, mediated by the post-feeding increase in amino acid levels. We have previously shown that the rise in the amino acid leucine, alone in the blood after a meal, increases protein synthesis in skeletal muscle. Our work further identified the intracellular signaling proteins that respond to leucine in skeletal muscle. We also showed that the stimulation of protein synthesis in skeletal muscle in response to provision of leucine is quite transient unless the supply of other amino acids is maintained. Furthermore, the response to leucine decreases with age. This information furthers the scientific understanding of the mechanisms underlying the response of different parts of the body to nourishment, and will help us find optimal ways of supporting the proper growth and development of babies.
Technical Abstract: We have previously shown that a physiological increase in plasma leucine for 60 and 120 min increases translation initiation factor activation in muscle of neonatal pigs. Although muscle protein synthesis is increased by leucine at 60 min, it is not maintained at 120 min, perhaps because of the decrease in plasma amino acids (AA). In the present study, 7- and 26-day-old pigs were fasted overnight and infused with leucine (0 or 400 micromol.kg(-1).h(-1)) for 120 min to raise leucine within the postprandial range. The leucine was infused in the presence or absence of a replacement AA mixture (without leucine) to maintain baseline plasma AA levels. AA administration prevented the leucine-induced reduction in plasma AA in both age groups. At 7 days, leucine infusion alone increased eukaryotic initiation factor (eIF) 4E binding protein-1 (4E-BP1) phosphorylation, decreased inactive 4E-BP1.eIF4E complex abundance, and increased active eIF4G.eIF4E complex formation in skeletal muscle; leucine infusion with replacement AA also stimulated these, as well as 70-kDa ribosomal protein S6 kinase, ribosomal protein S6, and eIF4G phosphorylation. At 26 days, leucine infusion alone increased 4E-BP1 phosphorylation and decreased the inactive 4E-BP1.eIF4E complex only; leucine with AA also stimulated these, as well as 70-kDa ribosomal protein S6 kinase and ribosomal protein S6 phosphorylation. Muscle protein synthesis was increased in 7-day-old (+60%) and 26-day-old (+40%) pigs infused with leucine and replacement AA but not with leucine alone. Thus the ability of leucine to stimulate eIF4F formation and protein synthesis in skeletal muscle is dependent on AA availability and age.