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

Abstract

Purpose of review: To highlight recent studies that 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.

Recent findings: Ingestion of a leucine-enriched essential amino acid nutrient solution rapidly and potently activates the mammalian target of rapamycin 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.

Summary: Leucine and essential amino acids appear to stimulate human muscle protein synthesis primarily by activating the mammalian target of rapamycin signalling pathway. How human muscle cells sense an increase in leucine and/or essential amino acids to activate mammalian target of rapamycin signalling is currently unknown. Recent work, however, 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).

Figure 1

Independent and combined effects of resistance exercise and leucine-enriched essential amino acid and carbohydrate (EAA+CHO) ingestion on muscle protein synthesis. Data are taken from three separate publications [32;42;43]. Baseline is the rate of muscle protein synthesis following an overnight fast in 13 young male subjects. Exercise data is the rate of muscle protein synthesis 2 hours following a bout of heavy leg resistance exercise (10 sets × 10 repetitions at 70% of 1-repetition maximum) in 7 young males. EAA+CHO is the rate of muscle protein synthesis 1 hour following the ingestion of a leucine-enriched EAA+CHO solution in 6 young males. The Exercise + EAA+CHO data is the rate of muscle protein synthesis 2 hours post-exercise when EAA+CHO was ingested at 1 hour following resistance exercise in 6 male subjects. Data are expressed as mean ± SE. *P<0.05 vs. Basal; #P<0.05 vs. 2 hr Post (Exercise).