Metabolic Advantage of 25(OH)D₃ versus 1,25(OH)₂D₃ Supplementation in Infantile Nephropathic Cystinosis-Associated...

Manifestations of infantile nephropathic cystinosis (INC) often include cachexia and deficiency of circulating vitamin D metabolites. We examined the impact of 25(OH)D₃ versus 1,25(OH)₂D₃ repletion in Ctns null mice, a mouse model of INC. Six weeks of intraperitoneal administration of 25(OH)D₃ (75 μg/kg/day) or 1,25(OH)₂D₃ (60 ng/kg/day) resulted in Ctns mice corrected low circulating 25(OH)D₃ or 1,25(OH)₂D₃ concentrations. While 25(OH)D₃ administration in Ctns mice normalized several metabolic parameters characteristic of cachexia as well as muscle function in vivo, 1,25(OH)₂D₃ did not. Administration of 25(OH)D₃ in Ctns mice increased muscle fiber size and decreased fat infiltration of skeletal muscle, which was accompanied by a reduction of abnormal muscle signaling pathways. 1,25(OH)₂D₃ administration was not as effective. In conclusion, 25(OH)D₃ supplementation exerts metabolic advantages over 1,25(OH)₂D₃ supplementation by amelioration of muscle atrophy and fat browning in Ctns mice.