Vitamin D Ameliorates Skeletal Muscle Atrophy After Spinal Cord Injury by Upregulating TIGAR and Enhancing Mitochondrial Function

ABSTRACT Background Skeletal muscle atrophy following spinal cord injury (SCI) is a debilitating secondary complication with no effective treatment. This study aimed to investigate the therapeutic efficacy of vitamin D (VD) in SCI‐induced muscle atrophy and to elucidate the underlying molecular mechanisms. Methods SCI patients' serum VD levels were measured, and muscle mass was assessed using dual‐energy X‐ray examination. Adult male C57BL/6 mice underwent a complete T10 spinal cord transection or sham surgery. On Day 3 post‐injury, mice received daily oral gavage of either VD (150 IU/kg) or vehicle (coconut oil) for 25 days. Body weight and motor function were assessed, and muscle‐specific parameters including hindlimb circumference, muscle mass, fibre cross‐sectional area (CSA) and fibre type composition were evaluated. Quantitative proteomics, Western blotting, and transmission electron microscopy (TEM) were further employed to investigate the molecular mechanisms in the gastrocnemius muscle. Results Serum VD level showed a significant positive correlation with the muscle index ( R 2  = 0.6495, p  p  p  p  p  p  p  p   Conclusion VD mitigates skeletal muscle atrophy following SCI by restoring metabolic and mitochondrial homeostasis through the upregulation of TIGAR. Our findings establish a strong preclinical rationale for investigating VD supplementation as a therapeutic strategy to preserve muscle health in SCI patients.