Differential regulation of protein synthesis in skeletal muscle and liver of neonatal pigs by leucine through an mTORC1-dependent pathway

• Published in: Journal of animal science and biotechnology 2012-02, Vol.3 (1), p.32-41, Article 3
• Main Authors: Suryawan, Agus, Nguyen, Hanh V, Almonaci, Rosemarie D, Davis, Teresa A
• Format: Article
• Language: English
• Subjects: AKT protein; Amino acids; AMP-activated protein kinase; Antibodies; Cell culture; Elongation; Hogs; In vivo methods and tests; Initiation factor eIF-2α; Insulin; Kinases; Laboratory animals; Leucine; Liver; mechanism of action; messenger RNA; Mode of action; mRNA; mTORC1; muscle protein; Muscles; Musculoskeletal system; neonatal pigs; Neonates; Phosphorylation; Physiology; piglets; Protein biosynthesis; Protein synthesis; Proteins; Rapamycin; Ribosomal protein S6; Ribosomal protein S6 kinase; Sensitivity enhancement; Skeletal muscle; TOR protein; translation (genetics); 亮氨酸; 合成率; 新生儿; 猪肝脏; 蛋白激酶B; 雷帕霉素; 骨骼肌; 高蛋白质
• ISSN: 1674-9782; 2049-1891; 2049-1891
• DOI: 10.1186/2049-1891-3-3

Neonatal growth is characterized by a high protein synthesis rate that is largely due to an enhanced sensitivity to the postprandial rise in insulin and amino acids, especially leucine. The mechanism of leucine＇s action in vivo is not well understood. In this study, we investigated the effect of leucine infusion on protein synthesis in skeletal muscle and liver of neonatal pigs. To evaluate the mode of action of leucine, we used rapamycin, an inhibitor of mammalian target of rapamycin （mTOR） complex-1 （mTORC1）. Overnight-fasted 7-day-old piglets were treated with rapamycin for 1 hour and then infused with leucine （400 μmol·kg^-1·h^-1） for 1 hour. Leucine infusion increased the rate of protein synthesis, and ribosomal protein S6 kinase 1 （S6K1） and eukaryotic initiation factor （elF） 4E-binding protein-1 （4E-BP1） phosphorylation in gastrocnemius and masseter muscles （P 〈 0.05）, but not in the liver. The leucine-induced stimulation of protein synthesis and S6K1 and 4E-BP1 phosphorylation were completely blocked by rapamycin, suggesting that leucine action is by an mTORC1-dependent mechanism. Neither leucine nor rapamycin had any effect on the activation of the upstream mTQRC1 regulators, AMP-activated protein kinase and protein kinase B, in skeletal muscle or liver. The activation of elF2α and elongation factor 2 was not affected by leucine or rapamycin, indicating that these two pathways are not limiting steps of leucine-induced protein synthesis. These results suggest that leucine stimulates muscle protein synthesis in neonatal pigs by inducing the activation of mTORC1 and its downstream pathway leading to mRNA translation.