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The Role of mTOR in Mechanical Load Induced Skeletal Muscle Hypertrophy and Hyperplasia
Author(s) -
Hornberger Troy A.,
Mabrey Danielle M.,
Frey John W.,
Lincoln Hannah C.,
You JaeSung,
Jacobs Brittany L.,
Goodman Craig A.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1105.1
Subject(s) - pi3k/akt/mtor pathway , skeletal muscle , muscle hypertrophy , sirolimus , hyperplasia , rptor , mechanistic target of rapamycin , endocrinology , medicine , chemistry , microbiology and biotechnology , pharmacology , cancer research , biology , signal transduction
Placing a chronic mechanical load on skeletal muscle induces a hypertrophic response and several studies have demonstrated that systemic administration of rapamycin will block this event. Since rapamycin is considered to be a highly specific inhibitor of mTOR, it has been widely concluded that mTOR is the rapamycin‐sensitive element that confers the hypertrophic effects of mechanical loading. However, like most pharmacological inhibitors, rapamycin can exert non‐specific (mTOR‐independent) actions. Furthermore, systemic administration of rapamycin would be expected to inhibit mTOR signaling in all cells throughout the body, and therefore, it is not clear if the anti‐hypertrophic effects of rapamycin are specifically due to inhibition of mTOR signaling in skeletal muscle cells. To address these points, we have employed transgenic mice with muscle specific expression of various rapamycin‐resistant mutants of mTOR. With these mice we have confirmed that mTOR is the rapamycin‐sensitive element, in skeletal muscle, that confers mechanical load induced hypertrophy, and that mTOR kinase activity is necessary for this event. Furthermore, the mechanical loading model employed in this study (synergist ablation) induced robust hyperplasia (59% increase in fiber number after 14 days), but surprisingly, the hyperplasia was elicited through an mTOR‐independent mechanism.