Metabolic Advantage of 25(OH)D 3 versus 1,25(OH) 2 D 3 Supplementation in Infantile Nephropathic Cystinosis-Associated Adipose Tissue Browning and Muscle Wasting.

Manifestations of infantile nephropathic cystinosis (INC) often include cachexia and deficiency of circulating vitamin D metabolites. We examined the impact of 25(OH)D 3 versus 1,25(OH) 2 D 3 repletion in Ctns null mice, a mouse model of INC. Six weeks of intraperitoneal administration of 25(OH)D 3 (75 μg/kg/day) or 1,25(OH) 2 D 3 (60 ng/kg/day) resulted in Ctns -/- mice corrected low circulating 25(OH)D 3 or 1,25(OH) 2 D 3 concentrations. While 25(OH)D 3 administration in Ctns -/- mice normalized several metabolic parameters characteristic of cachexia as well as muscle function in vivo, 1,25(OH) 2 D 3 did not. Administration of 25(OH)D 3 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) 2 D 3 administration was not as effective. In conclusion, 25(OH)D 3 supplementation exerts metabolic advantages over 1,25(OH) 2 D 3 supplementation by amelioration of muscle atrophy and fat browning in Ctns -/- mice.