Vitamin D Deficiency Accelerates Limited Activity-induced Skeletal Muscle Atrophy Via FOXO3a-mediated Protein Degradation

Objective: Serum vitamin D levels in the population are closely related to skeletal muscle mass and function.Animal experiments have also shown that long-term vitamin D deficiency leads to decreased skeletal muscle mass,but the effect of vitamin D levels on skeletal muscle atrophy caused by immobilized has not been studied.The primary objective of this study was to investigate the effects of vitamin D deficiency or 1,25(OH)2D3(1,25D)-supplements on skeletal muscle atrophy induced by activity limitation.Methods: Male 4-week-old C57BL/6J mice were fed a vitamin D-deficient and 1,25-dihydroxy vitamin D3(1,25D)-added purified diet for 24 weeks before immobilized.Skeletal muscle atrophy level was determined by mouse grip force,gastrocnemius(GA)muscle mass and muscle fiber cross-sectional area(CSA),and the expression levels of E3-ubiquitin ligase and FOXO3 a protein were detected.Results: Vitamin D deficiency accelerates decrease of GA muscle weight,muscle fiber CSA,and grip strength,and increased Mu RF1,MAFbx,and FOXO3 a protein expression in activity-limited-mice.In addition,1,25 D supplementation inhibits reduced grip strength induced by limited-activity.Conclusion: Vitamin D deficiency in mice is mediated by FOXO3a-mediated E3-ubiquitin ligase pathway aggravation of skeletal muscle atrophy caused by immobilized.Interestingly,the effect of vitamin D on grip force is dependent on activity levels and can only be seen when activity limitation.This is important for people who are prone to limited activity or lack of activity,such as older adults,to avoid vitamin D deficiency.