Differential regulation of protein synthesis in skeletal muscle and liver of neonatal pigs by leucine through an mTORC1-dependent pathway
<p>Abstract</p> <p>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 <it>in vivo </it>is not we...
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| Format: | Article |
| Language: | English |
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BMC
2012-02-01
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| Series: | Journal of Animal Science and Biotechnology |
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| Online Access: | http://www.jasbsci.com/content/3/1/3 |
| _version_ | 1818583489583251456 |
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| author | Suryawan Agus Nguyen Hanh V Almonaci Rosemarie D Davis Teresa A |
| author_facet | Suryawan Agus Nguyen Hanh V Almonaci Rosemarie D Davis Teresa A |
| author_sort | Suryawan Agus |
| collection | DOAJ |
| description | <p>Abstract</p> <p>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 <it>in vivo </it>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<sup>-1</sup>·h<sup>-1</sup>) for 1 hour. Leucine infusion increased the rate of protein synthesis, and ribosomal protein S6 kinase 1 (S6K1) and eukaryotic initiation factor (eIF) 4E-binding protein-1 (4E-BP1) phosphorylation in gastrocnemius and masseter muscles (<it>P </it>< 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 mTORC1 regulators, AMP-activated protein kinase and protein kinase B, in skeletal muscle or liver. The activation of eIF2α 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.</p> |
| first_indexed | 2024-12-16T08:06:06Z |
| format | Article |
| id | doaj.art-be14b1329ae64b7bb75a910953c6f109 |
| institution | Directory Open Access Journal |
| issn | 1674-9782 2049-1891 |
| language | English |
| last_indexed | 2024-12-16T08:06:06Z |
| publishDate | 2012-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Animal Science and Biotechnology |
| spelling | doaj.art-be14b1329ae64b7bb75a910953c6f1092022-12-21T22:38:28ZengBMCJournal of Animal Science and Biotechnology1674-97822049-18912012-02-0131310.1186/2049-1891-3-3Differential regulation of protein synthesis in skeletal muscle and liver of neonatal pigs by leucine through an mTORC1-dependent pathwaySuryawan AgusNguyen Hanh VAlmonaci Rosemarie DDavis Teresa A<p>Abstract</p> <p>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 <it>in vivo </it>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<sup>-1</sup>·h<sup>-1</sup>) for 1 hour. Leucine infusion increased the rate of protein synthesis, and ribosomal protein S6 kinase 1 (S6K1) and eukaryotic initiation factor (eIF) 4E-binding protein-1 (4E-BP1) phosphorylation in gastrocnemius and masseter muscles (<it>P </it>< 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 mTORC1 regulators, AMP-activated protein kinase and protein kinase B, in skeletal muscle or liver. The activation of eIF2α 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.</p>http://www.jasbsci.com/content/3/1/3leucinemTORC1neonatal pigsrapamycinskeletal muscle |
| spellingShingle | Suryawan Agus Nguyen Hanh V Almonaci Rosemarie D Davis Teresa A Differential regulation of protein synthesis in skeletal muscle and liver of neonatal pigs by leucine through an mTORC1-dependent pathway Journal of Animal Science and Biotechnology leucine mTORC1 neonatal pigs rapamycin skeletal muscle |
| title | Differential regulation of protein synthesis in skeletal muscle and liver of neonatal pigs by leucine through an mTORC1-dependent pathway |
| title_full | Differential regulation of protein synthesis in skeletal muscle and liver of neonatal pigs by leucine through an mTORC1-dependent pathway |
| title_fullStr | Differential regulation of protein synthesis in skeletal muscle and liver of neonatal pigs by leucine through an mTORC1-dependent pathway |
| title_full_unstemmed | Differential regulation of protein synthesis in skeletal muscle and liver of neonatal pigs by leucine through an mTORC1-dependent pathway |
| title_short | Differential regulation of protein synthesis in skeletal muscle and liver of neonatal pigs by leucine through an mTORC1-dependent pathway |
| title_sort | differential regulation of protein synthesis in skeletal muscle and liver of neonatal pigs by leucine through an mtorc1 dependent pathway |
| topic | leucine mTORC1 neonatal pigs rapamycin skeletal muscle |
| url | http://www.jasbsci.com/content/3/1/3 |
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