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.

The role of raptor in the mechanical load‐induced regulation of mTOR signaling, protein synthesis, and skeletal muscle hypertrophy

“…Previous studies have shown that a subset of mTORC1-dependent, but not mTORC2-dependent, signaling events are highly sensitive to inhibition by rapamycin (10)(11)(12). For this reason, it has been widely assumed that mTORC1 is responsible for the RSmTOR-dependent signaling events that control mechanical load-induced hypertrophy (13,14). However, a growing body of evidence has raised concerns about this assumption.…”

Efeito de diferentes doses de nandrolona associado ao treinamento de força sobre o perfil fenotípico e área de secção transversa do músculo de ratos

“…De forma geral, repetidas sessões de treinamento de força realizados em ratos ou humanos, promovem adaptações nas fibras musculares por meio de alterações do conteúdo protéico intramuscular (síntese protéica), resultando no aumento da área de secção transversa (AST) da musculatura esquelética e adaptações no fenótipo das fibras (transição das fibras) [5][6][7] .…”

Signaling Pathways that Mediate Skeletal Muscle Hypertrophy: Effects of Exercise Training

“…Thus, mechanical signal transduction is also capable of inducing growth by means of a mechanism other than growth factor signaling, which is independent of upstream elements such as IGFI and PI3K [28] The strength training consists of mechanical stimuli and is a potent agent that increases tropism in the skeletal muscle. This increase is triggered by increase in IGFI or MGF (mechano growth factor) protein expression which leads to a sequential activation cascade, ordered by PI3K, PDKI and II (phosphoinositide dependent kinase I and II) and Akt.…”