Alterations in energy expenditure and muscle performance following short-term muscle immobilization and rehabilitative exercise in mice.

PURPOSE: This study aimed to investigate the systemic metabolic and functional consequences of short-term hindlimb immobilization and to determine the role of rehabilitative exercise in facilitating recovery of muscle mass, function and whole-body energy metabolism. METHODS: Male ICR mice (n = 20) underwent 2 weeks of unilateral hindlimb immobilization, followed by 2 weeks of recovery with (n = 10) or without (n = 10) treadmill-based rehabilitative exercise. Whole-body energy metabolism (oxygen uptake, carbon dioxide production, respiratory exchange ratio, carbohydrate oxidation, fat oxidation, energy expenditure) was measured with body composition, grip strength, and gait analysis at three points: pre-immobilization, post-immobilization, and recovery. RESULTS: Immobilization induced significant reductions in body weight, lean mass, grip strength, and stride length, confirming rapid onset of immobilization-induced muscle atrophy. Paradoxically, despite the reduction in muscle mass and function, immobilization increased oxygen uptake, carbon dioxide production, fat oxidation, and energy expenditure, while reducing the respiratory exchange ratio. During recovery, exercise promoted lean mass restoration, increased grip strength and improved gait performance compared with passive recovery. Exercise also maintained carbohydrate utilization and energy expenditure, counteracting the decline observed in the passive recovery group. CONCLUSION: Short-term immobilization induces both structural and functional impairments and maladaptive systemic metabolic alteration such as enhanced fat oxidation and increased energy cost due to potential inefficiency. In contrast, rehabilitative exercise effectively restores muscle mass and function and supports metabolic flexibility. These findings underscore the importance of early low-intensity exercise as a strategy to preserve muscular and metabolic health during recovery from muscle immobilization.