Leucine-enriched nutrients and the regulation of mammalian target of rapamycin signalling and human skeletal muscle protein synthesis

Abstract

To highlight recent studies which have examined the cell signalling mechanisms responsible for the amino acid (primarily leucine and the essential amino acids) stimulation of human skeletal muscle protein synthesis. Ingestion of a leucine-enriched essential amino acid nutrient solution rapidly and potently activates the mammalian target of rapamycin (mTOR) signalling pathway and protein synthesis in human skeletal muscle. Further, mTOR signalling and muscle protein synthesis are enhanced when leucine-enriched nutrients are ingested following resistance exercise. The addition of leucine to regular meals may improve the ability of feeding to stimulate protein synthesis in old human muscle. Leucine and essential amino acids appear to stimulate human muscle protein synthesis primarily by activating the mTOR signalling pathway. How human muscle cells sense an increase in leucine and/or essential amino acids to activate mTOR signalling is currently unknown. However, recent work suggests that the kinases hVps34 and MAP43K may be involved. Leucine-enriched essential amino acid ingestion, in combination with resistance exercise in some cases, may be a useful intervention to promote mTOR signalling and protein synthesis in an effort to counteract a variety of muscle wasting conditions (e.g. sarcopenia, cachexia, AIDS, inactivity/bed-rest, sepsis, kidney failure, and trauma).