A hypothesis for a possible synergy between ghrelin and exercise in patients with cachexia: Biochemical and physiological bases

This article reviews the biochemical and physiological observations underpinning the synergism between ghrelin and ghrelin agonists with exercise, especially progressive resistance training that has been shown to increase muscle mass. The synergy of ghrelin agonists and physical exercise could be beneficial in conditions where muscle wasting is present, such as that found in patients with advanced cancer. The principal mechanism that controls muscle anabolism following the activation of the ghrelin receptor in the central nervous system involves the release of growth hormone/insulin-like growth factor-1 (GH/IGF-1). GH/IGF-1 axis has a dual pathway of action on muscle growth: (a) a direct action on muscle, bone and fat tissue and (b) an indirect action via the production of both muscle-restricted mIGF-1 and anti-cachectic cytokines. Progressive resistance training is a potent inducer of the secretion the muscle-restricted IGF-1 (mIGF-1) that enhances protein synthesis, increases lean body mass and eventually leads to the improvement of muscle strength. Thus, the combination of ghrelin administration with progressive resistance training may serve to circumvent ghrelin resistance and further reduce muscle wasting, which are commonly associated with cachexia.