Working around the clock: circadian rhythms and skeletal muscle

Center for Muscle Biology, Department of Physiology, University of Kentucky, Lexington, Kentucky Submitted 6 July 2009 ; accepted in final form 19 August 2009 The study of the circadian molecular clock in skeletal muscle is in the very early stages. Initial research has demonstrated the presence of the molecular clock in skeletal muscle and that skeletal muscle of a clock-compromised mouse, Clock mutant, exhibits significant disruption in normal expression of many genes required for adult muscle structure and metabolism. In light of the growing association between the molecular clock, metabolism, and metabolic disease, it will also be important to understand the contribution of circadian factors to normal metabolism, metabolic responses to muscle training, and contribution of the molecular clock in muscle-to-muscle disease (e.g., insulin resistance). Consistent with the potential for the skeletal muscle molecular clock modulating skeletal muscle physiology, there are findings in the literature that there is significant time-of-day effects for strength and metabolism. Additionally, there is some recent evidence that temporal specificity is important for optimizing training for muscular performance. While these studies do not prove that the molecular clock in skeletal muscle is important, they are suggestive of a circadian contribution to skeletal muscle function. The application of well-established models of skeletal muscle research in function and metabolism with available genetic models of molecular clock disruption will allow for more mechanistic understanding of potential relationships. molecular clock; Bmal1 ; MyoD ; peroxisome proliferator-activated receptor- coactivator-1 Address for reprint requests and other correspondence: K. A. Esser, Center for Muscle Biology, Dept. of Physiology, Chandler College of Medicine, Univ. of Kentucky, 800 Rose St., Lexington, KY 40536 (e-mail: kaesse2{at}uky.edu ).