Nutritional and contractile regulation of human skeletal muscle protein synthesis and mTORC1 signaling

Abstract

In this review we discuss current findings in the human skeletal muscle literature describing the acute influence of nutrients (leucine-enriched essential amino acids in particular) and resistance exercise on muscle protein synthesis and mammalian target of rapamycin complex 1 (mTORC1) signaling. We show that essential amino acids and an acute bout of resistance exercise independently stimulate human skeletal muscle protein synthesis. It also appears that ingestion of essential amino acids following resistance exercise leads to an even larger increase in the rate of muscle protein synthesis compared with the independent effects of nutrients or muscle contraction. Until recently the cellular mechanisms responsible for controlling the rate of muscle protein synthesis in humans were unknown. In this review, we highlight new studies in humans that have clearly shown the mTORC1 signaling pathway is playing an important regulatory role in controlling muscle protein synthesis in response to nutrients and/or muscle contraction. We propose that essential amino acid ingestion shortly following a bout of resistance exercise is beneficial in promoting skeletal muscle growth and may be useful in counteracting muscle wasting in a variety of conditions such as aging, cancer cachexia, physical inactivity, and perhaps during rehabilitation following trauma or surgery.

Cycle training induces muscle hypertrophy and strength gain: strategies and mechanisms

“…The translation of messenger ribonucleic acid (mRNA) plays a prominent role in protein synthesis following an exposure to exercise stimuli (43,61). In translation, the mechanistic target of rapamycin (mTOR) enhances mRNA translation through the phosphorylation of eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) and ribosomal protein S6 kinase 1(S6K1) (8,9,16,17), which in turn results in an increase in muscle protein synthesis. Several mitogen-activated protein kinase (MAPK) signaling pathways such as extracellular signal-regulated kinase (ERK) and p38-MAPK signaling pathways also play an important role in muscle protein synthesis (16,53).…”

Physiological stimuli necessary for muscle hypertrophy

“…Muscle protein synthesis can be enhanced by exercise stimuli through the following mechanisms: 1) exposure to exercise stimuli increasing the phosphorylation of the mechanistic target of rapamycin (mTOR), 2) increase in phosphorylation of the downstream targets of mTOR, i.e. eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) and ribosomal protein S6 kinase 1(S6K1), and 3) enhancement of mRNA translation (creation of proteins) [10][11][12][13][14][15] . Numerous attempts have been made to uncover ideal training conditions for muscle hypertrophy.…”

mTOR signaling response to resistance exercise is altered by chronic resistance training and detraining in skeletal muscle

“…However, resistance exercise also activates extracellular signal-regulated kinase (ERK) 1/2 and its downstream substrate p90 ribosomal S6 kinase (p90RSK), which are both involved in a signaling pathway independent of mTOR activity (6,22,29,42). The ERK signaling pathway is also considered to be a regulator of translation initiation and protein synthesis (12,13,39). Therefore, studies investigating mTOR and ERK signaling pathway activities should give insight into the mechanisms underlying resistance exercise-induced anabolic responses.…”