Gene Expression Testing Methods Quiz week 10

Activation of mTORC1 and Muscle Hypertrophy

• mTORC1 and mTORC2 are two distinct complexes, with mTORC1 being inhibited by rapamycin
• Following resistance exercise, mTORC1 activity increases and correlates with muscle mass gain
• Unlike growth factors, resistance exercise activates mTOR independently of PI3K
• Resistance exercise activates an unidentified kinase that phosphorylates TSC2, leading to mTORC1 activation
• Resistance exercise also increases amino acid uptake into the muscle, particularly leucine and glutamine
• Leucine activates mTORC1 by binding to LRS and RagD, leading to increased protein synthesis
• Resistance exercise activates mTORC1 through the activation of an RxRxx-directed kinase and enhanced amino acid uptake
• Inhibiting mTOR with rapamycin blocks muscle hypertrophy in mice and humans
• Mice with a rapamycin-resistant mutant of mTOR show muscle hypertrophy even in the presence of rapamycin
• This demonstrates that resistance exercise-induced muscle hypertrophy is completely dependent on mTOR
• The activation of mTORC1 by resistance exercise and protein feeding explains load-dependent activation and the effects of amino acid consumption on muscle hypertrophy
• Evidence suggests that mTORC1 is necessary for resistance exercise-induced muscle growth