Day-Night Oscillation of Atrogin1 and Timing-Dependent Preventive Effect of Weight-Bearing on Muscle Atrophy

• Published in: EBioMedicine 2018-11, Vol.37, p.499-508
• Main Authors: Aoyama, Shinya, Kojima, Shuichi, Sasaki, Keisuke, Ishikawa, Ryosuke, Tanaka, Mizuho, Shimoda, Takeru, Hattori, Yuta, Aoki, Natsumi, Takahashi, Kengo, Hirooka, Rina, Takizawa, Miku, Haraguchi, Atsushi, Shibata, Shigenobu
• Format: Article
• Language: English
• Subjects: Animals; Atrogin1; Chrono-exercise; Circadian Rhythm; Gene Expression Regulation; Hindlimb-unloading; Male; Mice; Mice, Inbred ICR; Mice, Mutant Strains; Muscle Proteins - biosynthesis; Muscle Proteins - genetics; Muscular Atrophy - genetics; Muscular Atrophy - metabolism; Muscular Atrophy - pathology; Muscular Atrophy - therapy; Physical Conditioning, Animal; Research paper; SKP Cullin F-Box Protein Ligases - biosynthesis; SKP Cullin F-Box Protein Ligases - genetics; Weight-Bearing
• ISSN: 2352-3964; 2352-3964
• DOI: 10.1016/j.ebiom.2018.10.057

Atrogin1, which is one of the key genes for the promotion of muscle atrophy, exhibits day-night variation. However, its mechanism and the role of its day-night variation are largely unknown in a muscle atrophic context. The mice were induced a muscle atrophy by hindlimb-unloading (HU). To examine a role of circadian clock, Wild-type (WT) and Clock mutant mice were used. To test the effects of a neuronal effects, an unilateral ablation of sciatic nerve was performed in HU mice. To test a timing-dependent effects of weight-bearing, mice were released from HU for 4 h in a day at early or late active phase (W-EAP and W-LAP groups, respectively). We found that the day-night oscillation of Atrogin1 expression was not observed in Clock mutant mice or in the sciatic denervated muscle. In addition, the therapeutic effects of weight-bearing were dependent on its timing with a better effect in the early active phase. These findings suggest that the circadian clock controls the day-night oscillation of Atrogin1 expression and the therapeutic effects of weight-bearing are dependent on its timing. Council for Science, Technology, and Innovation, SIP, “Technologies for creating next-generation agriculture, forestry, and fisheries”. •Atrogin1 expression shows day-night variation in a muscle atrophic context.•Preventive effects of intermittent weight-bearing on muscle loss are dependent on its timing.