Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/8/2005
Publication Date: 4/1/2006
Citation: Escobar, J., Frank, J.W., Suryawan, A., Nguyen, H.V., Kimball, S.R., Jefferson, L.S., Davis, T.A. 2006. Regulation of cardiac and skeletal muscle protein synthesis by individual branched-chain amino acids in neonatal pigs. American Journal Physiology-Endocrinology and Metabolism. 290(4):E612-E621. Interpretive Summary: Skeletal muscle grows at a very rapid rate in new-born pigs. This is due in part to higher sensitivity of skeletal muscle to make more proteins (protein synthesis) from substrates (amino acids) that are obtained after eating. Studies show that amino acids are not only substrates for protein synthesis, but also act as stimulator of protein synthesis. We have shown that leucine (a member of branched-chain amino acids/BCAA) alone can stimulate protein synthesis in skeletal muscle of new-born pigs; however, the effect of isoleucine and valine (other members of BCAA) has not been tested. Therefore, we examined the possible role of isoleucine and valine (as comparison, we used leucine) on the stimulation of skeletal muscle and heart muscle in new-born pigs. In this study we determine the effect of these amino acids on the stimulation of protein synthesis and the activation of protein synthesis mechanisms that allow skeletal muscle and heart muscle to make proteins (eIF-4EBP1, eIF-4G, S6K1 and rpS6). The results of this study show that leucine, but not isoleucine or valine, stimulate protein synthesis and induce the activation of protein synthesis mechanisms. In conclusion, the results of this study suggest that leucine, but not isoleucine or valine, gives skeletal muscle and heart muscle a signal so these muscles can make protein after piglets consumed meals.
Technical Abstract: Skeletal muscle grows at a very rapid rate in the neonatal pig, due in part to an enhanced sensitivity of protein synthesis to the postprandial rise in amino acids. An increase in leucine alone stimulates protein synthesis in skeletal muscle of the neonatal pig; however, the effect of isoleucine and valine has not been investigated in this experimental model. The left ventricular wall of the heart grows faster than the right ventricular wall during the first 10 days of postnatal life in the pig. Therefore, the effects of individual BCAA on protein synthesis in individual skeletal muscles and in the left and right ventricular walls were examined. Fasted pigs were infused with 0 or 400 micromol.kg(-1).h(-1) leucine, isoleucine, or valine to raise individual BCAA to fed levels. Fractional rates of protein synthesis and indexes of translation initiation were measured after 60 min. Infusion of leucine increased (P < 0.05) phosphorylation of eukaryotic initiation factor (eIF)4E-binding protein-1 and increased (P < 0.05) the amount and phosphorylation of eIF4G associated with eIF4E in longissimus dorsi and masseter muscles and in both ventricular walls. Leucine increased (P < 0.05) the phosphorylation of ribosomal protein (rp)S6 kinase and rpS6 in longissimus dorsi and masseter but not in either ventricular wall. Leucine stimulated (P < 0.05) protein synthesis in longissimus dorsi, masseter, and the left ventricular wall. Isoleucine and valine did not increase translation initiation factor activation or protein synthesis rates in skeletal or cardiac muscles. The results suggest that the postprandial rise in leucine, but not isoleucine or valine, acts as a nutrient signal to stimulate protein synthesis in cardiac and skeletal muscles of neonates by increasing eIF4E availability for eIF4F complex assembly.