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

Shinya Aoyama, Shuichi Kojima, Keisuke Sasaki, Ryosuke Ishikawa, Mizuho Tanaka, Takeru Shimoda, Yuta Hattori, Natsumi Aoki, Kengo Takahashi, Rina Hirooka, Miku Takizawa, Atsushi Haraguchi, Shigenobu Shibata

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: 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. Methods: 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). Findings: 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. Interpretation: 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. Fund: Council for Science, Technology, and Innovation, SIP, “Technologies for creating next-generation agriculture, forestry, and fisheries”.

Original languageEnglish
JournalEBioMedicine
DOIs
Publication statusAccepted/In press - 2018 Jan 1

Keywords

  • Atrogin1
  • Chrono-exercise
  • Circadian rhythm
  • Hindlimb-unloading
  • Weight-bearing

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Aoyama, S., Kojima, S., Sasaki, K., Ishikawa, R., Tanaka, M., Shimoda, T., Hattori, Y., Aoki, N., Takahashi, K., Hirooka, R., Takizawa, M., Haraguchi, A., & Shibata, S. (Accepted/In press). Day-Night Oscillation of Atrogin1 and Timing-Dependent Preventive Effect of Weight-Bearing on Muscle Atrophy. EBioMedicine. https://doi.org/10.1016/j.ebiom.2018.10.057