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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 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
Pages (from-to)499-508
Number of pages10
JournalEBioMedicine
Volume37
DOIs
Publication statusPublished - 2018 Nov

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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