Day-Night Oscillation of Atrogin1 and Timing-Dependent Preventive Effect of Weight-Bearing on Muscle AtrophyResearch in context
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
Affiliations
Shinya Aoyama
Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan,; Organization for University Research Initiatives, Waseda University, Tokyo, Japan
Shuichi Kojima
Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan,
Keisuke Sasaki
Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan,
Ryosuke Ishikawa
Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan,
Mizuho Tanaka
Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan,
Takeru Shimoda
Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan,
Yuta Hattori
Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan,
Natsumi Aoki
Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan,; Organization for University Research Initiatives, Waseda University, Tokyo, Japan
Kengo Takahashi
Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan,
Rina Hirooka
Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan,
Miku Takizawa
Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan,
Atsushi Haraguchi
Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan,
Shigenobu Shibata
Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan,; Corresponding author at: Wakamatsu-cho 2-2, Tokyo 162-8480, Japan.
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”. Keywords: Circadian rhythm, Chrono-exercise, Atrogin1, Hindlimb-unloading, Weight-bearing