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Delayed recovery of skeletal muscle mass following hindlimb immobilization in mTOR heterozygous mice
Author(s) -
Lang Susan M.,
Kazi Abid A.,
Hong-Brown Ly,
Lang Charles H.
Publication year - 2012
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.26.1_supplement.715.1
Subject(s) - pi3k/akt/mtor pathway , medicine , hindlimb , endocrinology , muscle atrophy , skeletal muscle , soleus muscle , chemistry , protein degradation , protein turnover , atrophy , protein biosynthesis , biology , biochemistry , signal transduction
The role of mTOR in regulating muscle protein balance was assessed in WT and mTOR heterozygous (+/−) mice after hindlimb immobilization and recovery, with data compared to the contralateral muscle. A gradual loss of muscle mass, which plateaued by day 7, was seen in WT mice. This response was associated with a sustained reduction in protein synthesis and increased proteasome activity. Atrogin‐1 and MuRF‐1 mRNA was transiently increased but returned to control values by day 7. The decreased muscle mass and protein synthesis and increased proteasome activity did not differ between WT and mTOR +/− mice after immobilization. After 10 days of recovery, WT mice showed no decrement in muscle mass and this accretion resulted from a sustained increase in protein synthesis and normalization of proteasome activity. In contrast, mTOR +/− mice failed to fully replete muscle mass. This defect was caused solely by the lack of a compensatory increase in protein synthesis. Delayed regrowth of the previously immobilized muscle in mTOR +/− mice was associated with a sustained inflammatory response the recovery period as well as a failure to increase IGF‐I. These data suggest mTOR activity is relatively more important in regulating the accretion of muscle mass during recovery than the loss of muscle during the atrophy phase, and that protein synthesis is more sensitive than degradation to the reduction in mTOR during muscle regrowth. (GM38021)