title: Mechanotransduction pathways in skeletal muscle hypertrophy.
abstract: In the last decade, molecular biology has contributed to define some of the cellular events that trigger skeletal muscle hypertrophy. Recent evidence shows that insulin like growth factor 1/phosphatidyl inositol 3-kinase/protein kinase B (IGF-1/PI3K/Akt) signaling is not the main pathway towards load-induced skeletal muscle hypertrophy. During load-induced skeletal muscle hypertrophy process, activation of mTORC1 does not require classical growth factor signaling. One potential mechanism that would activate mTORC1 is increased synthesis of phosphatidic acid (PA). Despite the huge progress in this field, it is still early to affirm which molecular event induces hypertrophy in response to mechanical overload. Until now, it seems that mTORC1 is the key regulator of load-induced skeletal muscle hypertrophy. On the other hand, how mTORC1 is activated by PA is unclear, and therefore these mechanisms have to be determined in the following years. The understanding of these molecular events may result in promising therapies for the treatment of muscle-wasting diseases. For now, the best approach is a good regime of resistance exercise training. The objective of this point-of-view paper is to highlight mechanotransduction events, with focus on the mechanisms of mTORC1 and PA activation, and the role of IGF-1 on hypertrophy process.
authors.affiliation: Departamento de Ciências Fisiológicas, Universidade Federal de São Carlos, São Carlos, São Paulo, Brasil. yamadaak@gmail.com
authors.forename: André Katayama
authors.initials: AK
authors.lastname: Yamada
authors.forename: Rozangela
authors.initials: R
authors.lastname: Verlengia
authors.forename: Carlos Roberto
authors.initials: CR
authors.lastname: Bueno Junior
mesh_terms: D006984:Hypertrophy / Q000473:pathology; D000076222:Mechanistic Target of Rapamycin Complex 1; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D046912:Multiprotein Complexes; D009122:Muscle Hypertonia / Q000378:metabolism* / Q000473:pathology*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology*; D010712:Phosphatidic Acids / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013314:Stress, Mechanical; D058570:TOR Serine-Threonine Kinases
chemical_list: D046912:Multiprotein Complexes; D010712:Phosphatidic Acids; D011506:Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases