Exercise Mimetics: Fact Or Fantasy?

Abstract

The abundant health benefits of physical exercise are not being translated into practice. In an effort to short circuit the need for physical activity to promote health, exercise-mimetic agents are being developed; they mimic the action of peptide molecules released from exercised muscles. The intention is to mimic biochemical responses even without performing exercise. Technologies have advanced to identify various exercise-induced proteins, called myokines, and to develop ligands which bind to the myokine receptors. A number of such chemicals exist that mimic the effects of activating Peroxisome proliferator-activated receptor-γ (PPARγ) coactivator 1α (PGC-1 α), Peroxisome proliferator-activated receptor β/δ (PPAR β/δ) and AMP-activated protein kinase (AMPK). Most such agents were tested in animal models with varying degrees of success and mostly undesirable adverse effects. The increasing complexity of exercise response is being recognized, making the development and use of single 'exercise-mimetics' ineffective, except for some narrow indications. In addition, some of the performance enhancing exercise-mimetics are being misused by endurance athletes, with the chemicals being banned as doping agents. In a fascinating interaction between physiology and pharmacology, agents that can mimic the beneficial effects of physical exercise are an enticing possibility over the distant horizon.