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Journal of Animal Science Abstract - Growth and Developmental Biology

Leucine stimulates mammalian target of rapamycin signaling in C2C12 myoblasts in part through inhibition of adenosine monophosphate-activated protein kinase1


This article in

  1. Vol. 85 No. 4, p. 919-927
    Received: May 26, 2006
    Accepted: Dec 11, 2006
    Published: December 8, 2014

    2 Corresponding author(s):

  1. M. Du2,
  2. Q. W. Shen,
  3. M. J. Zhu and
  4. S. P. Ford
  1. Department of Animal Science, University of Wyoming, Laramie 82071


Mammalian target of rapamycin (mTOR) signaling is one of the main signaling pathways controlling protein synthesis. Leucine treatment upregulates mTOR signaling, which enhances protein synthesis; however, the mechanisms are not well understood. Herein, treatment of C2C12 myoblast cells with leucine enhanced the phosphorylation of mTOR and ribosomal protein S6 kinase. Leucine treatment also decreased the adenosine monophosphate/ATP ratio in myoblasts by 36.4 ± 9.1% (P < 0.05) and reduced the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) α subunit at Thr172 (28.6 ± 4.9% reduction, P < 0.05) and inhibited AMPK activity (43.6 ± 3.5% reduction, P < 0.05). In addition, leucine increased the phosphorylation of mTOR at Ser2448 by 63.5 ± 10.0% (P < 0.05) and protein synthesis by 30.6 ± 6.1% (P < 0.05). Applying 5-aminoimidazole-4-carbox-amide 1-beta-d-ribonucleoside, an activator of AMPK, abolished the stimulation of mTOR signaling by leucine, showing that AMPK negatively controls mTOR signaling. To further show the role of AMPK in mTOR signaling, myoblasts expressing a dominant negative AMPKα subunit were employed. Negative myoblasts had very low AMPK activity. The activation of mTOR induced by leucine in these cells was abated, showing that AMPK contributed to mTOR activation. In conclusion, leucine stimulates mTOR signaling in part through AMPK inhibition. This study implicates AMPK as an important target for nutritional management to enhance mTOR signaling and protein synthesis in muscle cells, thereby increasing muscle growth.

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