Circadian regulation of muscle growth independent of locomotor activity
- Kelu, J.J., Pipalia, T.G., Hughes, S.M.
- Proceedings of the National Academy of Sciences of the United States of America 117(49): 31208-31218 (Journal)
- Registered Authors
- Hughes, Simon M.
- circadian rhythm, muscle, zebrafish
- MeSH Terms
- Circadian Clocks/drug effects
- Circadian Clocks/genetics*
- Circadian Rhythm/drug effects
- Circadian Rhythm/genetics*
- Larva/growth & development
- Locomotion/drug effects
- Mechanistic Target of Rapamycin Complex 1/genetics
- Muscle Development/genetics
- Muscle, Skeletal/growth & development*
- Muscle, Skeletal/metabolism
- Zebrafish/growth & development
- 33229575 Full text @ Proc. Natl. Acad. Sci. USA
Kelu, J.J., Pipalia, T.G., Hughes, S.M. (2020) Circadian regulation of muscle growth independent of locomotor activity. Proceedings of the National Academy of Sciences of the United States of America. 117(49):31208-31218.
Muscle tissue shows diurnal variations in function, physiology, and metabolism. Whether such variations are dependent on the circadian clock per se or are secondary to circadian differences in physical activity and feeding pattern is unclear. By measuring muscle growth over 12-h periods in live prefeeding larval zebrafish, we show that muscle grows more during day than night. Expression of dominant negative CLOCK (ΔCLK), which inhibits molecular clock function, ablates circadian differences and reduces muscle growth. Inhibition of muscle contraction reduces growth in both day and night, but does not ablate the day/night difference. The circadian clock and physical activity are both required to promote higher muscle protein synthesis during the day compared to night, whereas markers of protein degradation, murf messenger RNAs, are higher at night. Proteasomal inhibitors increase muscle growth at night, irrespective of physical activity, but have no effect during the day. Although physical activity enhances TORC1 activity, and the TORC1 inhibitor rapamycin inhibits clock-driven daytime growth, no effect on muscle growth at night was detected. Importantly, day/night differences in 1) muscle growth, 2) protein synthesis, and 3) murf expression all persist in entrained larvae under free-running constant conditions, indicating circadian drive. Removal of circadian input by exposure to either permanent darkness or light leads to suboptimal muscle growth. We conclude that diurnal variations in muscle growth and metabolism are a circadian property that is independent of, but augmented by, physical activity, at least during development.
Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes