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

• Published in: Journal of applied physiology (1985) Vol. 106; no. 4; pp. 1374 - 1384
• Main Authors: Drummond, Micah J, Dreyer, Hans C, Fry, Christopher S, Glynn, Erin L, Rasmussen, Blake B
• Format: Journal Article
• Language: English
• Published: United States Am Physiological Soc 01.04.2009; American Physiological Society
• Series: Regulation of Protein Metabolism in Exercise and Recovery
• Subjects: Aging - physiology; Amino acids; Exercise - physiology; Gene Expression; Highlighted Topic; Human subjects; Humans; Mechanistic Target of Rapamycin Complex 1; Multiprotein Complexes; Muscle Contraction - physiology; Muscle Proteins - biosynthesis; Muscle, Skeletal - metabolism; Muscle, Skeletal - physiology; Musculoskeletal system; Nutritional Physiological Phenomena - physiology; Protein Biosynthesis; Protein synthesis; Proteins; Signal transduction; Signal Transduction - physiology; Studies; TOR Serine-Threonine Kinases; Transcription Factors - physiology
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.91397.2008

1 Department of Physical Therapy, 2 Division of Rehabilitation Sciences, and 3 Sealy Center on Aging, University of Texas Medical Branch, Galveston, Texas Submitted 21 October 2008 ; accepted in final form 13 January 2009 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. essential amino acids; contraction; translation initiation; leucine Address for reprint requests and other correspondence: B. B. Rasmussen, Univ. of Texas Medical Branch, Dept. of Physical Therapy, Div. of Rehabilitation Sciences, 301 Univ. Blvd. Galveston, TX 77555-1144 (e-mail: blrasmus{at}utmb.edu )