Exercise Pills: At the Starting Line

Sedentary lifestyles, limited physical exercise, and prolonged inactivity undoubtedly increase chronic diseases, including obesity, type 2 diabetes, and cardiovascular diseases. It is widely acknowledged that exercise induces a number of physiological adaptations that have beneficial effects in the prevention and treatment of these chronic metabolic diseases. Unfortunately, exercise compliance is extremely low and often not possible. The development of exercise science and molecular techniques has increased our understanding of the molecular pathways responsive to exercise. Knowledge of these molecular targets has led to the development of chemical interventions that can mimic the beneficial effects of exercise without requiring actual muscle activity. This review focuses on the concept of ‘exercise pills’ and how they mimic the effects produced by physical exercise including oxidative fiber-type transformation, mitochondrial biogenesis, increased fat oxidation, angiogenesis, and improvement of exercise capacity. We also review candidate exercise pills, and contrast the beneficial effects and molecular mechanisms between physical exercise and exercise pills.

TrendsThe concept of ‘exercise pills’ has great potential for use in patients having low exercise compliance or in those for whom regular exercise is not feasible. Our increased understanding of the molecular targets of physical exercise makes it possible to design agents that mimic the physiological benefits of exercise.Current candidate exercise pills can be divided into three categories: pharmacological agonists (AICAR, GW501516, GSK4716, SR9009), hormones (MOTS-c, irisin), and phytochemicals [resveratrol and (–)-epicatechin].The signaling pathways of currently described exercise pills are outlined. None of the candidate exercise pills fully mimics the beneficial effects of exercise, but each exercise pill can activate distinct as well as overlapping target transcriptional regulators that can partly mimic the beneficial effects of physical exercise.