Circadian regulation of muscle growth independent of locomotor activity

Abstract

Muscle tissue shows circadian variation, but whether and how the intracellular circadian clock per se regulates muscle growth remains unclear. By measuring muscle growth over 12 h periods, here we show that muscle grows more during the day than at night. Inhibition of muscle contraction reduces growth to a similar extent in day and night, but does not ablate the circadian variation in growth. Muscle protein synthesis is higher during the day compared to night, whereas markers of protein degradation are higher at night. Mechanistically, the TORC1 inhibitor rapamycin inhibits the extra daytime growth, but no effect on muscle growth at night was detected. Conversely, the proteasomal inhibitor MG132 increases muscle growth at night, but has no effect during the day, irrespective of activity. Ablation of contractile activity rapidly reduces muscle protein synthesis both during the day and at night and leads to a gradual increase in Murf gene expression without ablating circadian variation in growth. Removal of circadian input by exposure to either permanent light or permanent darkness reduces muscle growth. We conclude that circadian variation in muscle growth is independent of the presence of, or changes in, physical activity and affects both protein synthesis and degradation in distinct circadian phases.