title: mTORC1 and the regulation of skeletal muscle anabolism and mass.
abstract: The mass and integrity of skeletal muscle is vital to whole-body substrate metabolism and health. Indeed, defects in muscle metabolism and functions underlie or exacerbate diseases like diabetes, rheumatoid arthritis, and cancer. Physical activity and nutrition are the 2 most important environmental factors that can affect muscle health. At the molecular level, the mammalian target of rapamycin complex 1 (mTORC1) is a critical signalling complex that regulates muscle mass. In response to nutrition and resistance exercise, increased muscle mass and activation of mTORC1 occur in parallel. In this review, we summarize recent findings on mTORC1 and its regulation in skeletal muscle in response to resistance exercise, alone or in combination with intake of protein or amino acids. Because increased activity of the complex is implicated in the development of muscle insulin resistance, obesity, and some cancers (e.g., ovarian, breast), drugs that target mTORC1 are being developed or are in clinical trials. However, various cancers are associated with extensive muscle wasting, due in part to tumour burden and malnutrition. This muscle wasting may also be a side effect of anticancer drugs. Because loss of muscle mass is associated not only with metabolic abnormalities but also dose limiting toxicity, we review the possible implications for skeletal muscle of long-term inhibition of mTORC1, especially in muscle wasting conditions.
authors.affiliation: School of Kinesiology and Health Science, Muscle Health Research Centre, York University, Toronto ON M3J 5P3, Canada. oadegoke@yorku.ca
authors.forename: Olasunkanmi A J
authors.initials: OA
authors.lastname: Adegoke
authors.forename: Abdikarim
authors.initials: A
authors.lastname: Abdullahi
authors.forename: Pegah
authors.initials: P
authors.lastname: Tavajohi-Fini
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001837:Body Weights and Measures; D004044:Dietary Proteins / Q000378:metabolism; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D009133:Muscular Atrophy / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D055070:Resistance Training / Q000379:methods; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases
chemical_list: D000596:Amino Acids; D004044:Dietary Proteins; D046912:Multiprotein Complexes; D009124:Muscle Proteins; D011506:Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases