LB070 - PRIOR DISUSE EXPOSURE ATTENUATES SKELETAL MUSCLE ATROPHY DURING SUBSEQUENT HINDLIMB UNLOADING IN MICE

LB070

PRIOR DISUSE EXPOSURE ATTENUATES SKELETAL MUSCLE ATROPHY DURING SUBSEQUENT HINDLIMB UNLOADING IN MICE

S. Inoue^1,*, A. Takemura², S. Fujita³

¹Research Organization of Science and Technology, Ritsumeikan University, Kusatsu, ²Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, ³Faculty of Sport and Health Science, Ritsumeikan University, Kusatsu, Japan

Rationale: Disuse-induced muscle atrophy often recurs in patients with chronic illness or recurrent hospitalization. Although the mechanisms of disuse atrophy have been extensively studied, whether prior disuse exposure modifies skeletal muscle responses to subsequent unloading remains unclear. This study examined the effects of prior disuse exposure on muscle mass and the regulation of protein synthesis and degradation during a subsequent unloading period.

Methods: Ten-week-old male C57BL/6J mice underwent 14 days of hindlimb unloading (HU) or remained as ground controls, followed by 42 days of reloading. Both groups then underwent a second bout of HU up to 7 days. An additional cohort underwent 14 days of unilateral hindlimb immobilization (IM), followed by 42 days of reloading and HU. The hindlimb muscles were collected at 0, 3, or 7 days of the second disuse phase. Protein synthesis and degradation signaling were assessed by western blotting.

Results: After 7 days of HU, the tibialis anterior muscle weight-to-body weight ratio decreased by 12–13% in mice without prior disuse exposure, whereas the decrease was limited to 7% and 9% in mice with prior HU and IM exposure, respectively (both P < 0.05). Puromycin incorporation was reduced during unloading but was unaffected by prior disuse exposure. mTORC1 downstream signaling was unchanged or reduced in previously atrophied muscles. In contrast, prior HU exposure attenuated unloading-induced increases in catabolic and autophagy-related markers, including Fbx32 and p62.

Conclusion: Prior disuse exposure attenuated the loss of tibialis anterior mass during subsequent unloading. This adaptation may be partly associated with attenuated activation of catabolic signaling rather than enhanced protein synthesis signaling. These findings indicate that prior disuse exposure induces persistent adaptations that alter skeletal muscle responses to subsequent unloading.

Disclosure of Interest: None declared