Regulation of mTOR by amino acids and resistance exercise in skeletal muscle.
Resistance exercise disturbs skeletal muscle homeostasis leading to activation of catabolic and anabolic processes within the muscle cell. A current challenge of exercise biology is to describe the molecular mechanisms of regulation by which contractile activity stimulates net protein breakdown during exercise and net protein synthesis during recovery. Muscle growth is optimized by combining exercise and appropriate nutritional strategies, such as amino acid (AA) and carbohydrate ingestion. The effects are integrated at the level of one central regulatory protein, mTOR (mammalian target of rapamycin). mTOR is a complex protein integrating signals of the energetic status of the cell and environmental stimuli to control protein synthesis, protein breakdown and therefore cell growth. mTOR is known to be activated by insulin, and the mechanisms involved are well documented. The ways by which exercise and AA lead to mTOR activation remain partially unclear. Exercise and AA use different signalling pathways upstream of mTOR. Exercise seems to recruit partially the same pathway as insulin, whereas AA could act more directly on mTOR. During resistance exercise, the activity of mTOR could be acutely blunted by AMP-activated protein kinase (AMPK), thus inhibiting protein synthesis and enhancing AA availability for energy metabolism. During recovery, the inhibition of mTOR by AMPK is suppressed, and its activation is maximized by the presence of AA. There appears to be a requirement for a minimal concentration of plasma insulin to stimulate muscle protein synthesis in response to resistance exercise and AA ingestion.
Deldicque
L
L
Institut d'Education Physique et de Réadaptation, Université catholique de Louvain, Belgium.
Theisen
D
D
Francaux
M
M
D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology; D000284:Administration, Oral; D000596:Amino Acids / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D019587:Dietary Supplements; D015444:Exercise / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D009119:Muscle Contraction / Q000502:physiology*; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000502:physiology*; D005082:Physical Exertion / Q000502:physiology; D014176:Protein Biosynthesis / Q000502:physiology; D011494:Protein Kinases / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases
D000596:Amino Acids; D009124:Muscle Proteins; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases