Circadian regulation of muscle growth independent of locomotor activity
| Autor: | Jeffrey J. Kelu, Simon M. Hughes, Tapan G. Pipalia |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
circadian rhythm
Muscle tissue medicine.medical_specialty Light muscle Photoperiod Circadian clock Mechanistic Target of Rapamycin Complex 1 Protein degradation Biology Muscle Development Muscle hypertrophy chemistry.chemical_compound 03 medical and health sciences 0302 clinical medicine Circadian Clocks Internal medicine MG132 medicine Animals Circadian rhythm Muscle Skeletal Zebrafish 030304 developmental biology Sirolimus 2. Zero hunger 0303 health sciences Multidisciplinary Cell Biology Biological Sciences zebrafish biology.organism_classification 3. Good health Endocrinology medicine.anatomical_structure chemistry Larva Darkness medicine.symptom Locomotion 030217 neurology & neurosurgery Muscle contraction |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.2012450117 |
| Popis: | Significance A long-standing question, particularly in physiotherapy and sports medicine, is whether time of day affects muscle metabolism and hence growth, either intrinsically or in response to exercise or nutrition. Answers would help to identify the best time of day to exercise, build muscle, and prevent aging- or disease-related sarcopenia. Here, we address this question in live zebrafish myotome in vivo, without interference from other circadian oscillations such as locomotor activity and food intake. We show that active muscle anabolizes more in the day and grows faster, while catabolizing more at night and growing slower. Such day/night differences remain in inactive muscle but disappear after clock disruption. We conclude that muscles display circadian differences in growth independent of activity and feeding. 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. |
| Databáze: | OpenAIRE |
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