Important role for AMPKαl in limiting skeletal muscle cell hypertrophy

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Abstract
Activation of AMP-activated protein kinase (AMPK) inhibits protein synthesis through the suppression of the mammalian target of rapamycin complex 1 (mTORC1), a critical regulator of muscle growth. The purpose of this investigation was to determine the role of the AMPKα1 catalytic subunit on muscle cell size control and adaptation to muscle hypertrophy. We found that AMPKα1(−/−) primary cultured myotubes and myofibers exhibit larger cell size compared with control cells in response to chronic Akt activation. We next subjected the plantaris muscle of AMPKα1(−/−) and control mice to mechanical overloading to induce muscle hypertrophy. We observed significant elevations of AMPKα1 activity in the control muscle at days 7 and 21 after the overload. Overloading-induced muscle hypertrophy was significantly accelerated in AMPKα1(−/−) mice than in control mice [+32 vs. +53% at day 7 and +57 vs. +76% at day 21 in control vs. AMPKα1(−/−) mice, respectively]. This enhanced growth of AMPKα1-deficient muscle was accompa...