期刊
CELLS
卷 11, 期 20, 页码 -出版社
MDPI
DOI: 10.3390/cells11203264
关键词
infantile nephropathic cystinosis; cachexia; adipose tissue browning; muscle wasting; vitamin D insufficiency; 25(OH)D-3; 1; 25(OH)(2)D-3
类别
资金
- Cystinosis Research Foundation
- Chunhui Plan Cooperative Scientific Research Project, Ministry of Education of the People's Republic of China [HLJ2019023]
- 2022 Key R&D Plan of Science and Technology Department of Sichuan Province [2022YFS0149]
- Science and Technology Fund of Chengdu Medical College in 2021 [CYZYB21-22]
- Medical Research Project of Sichuan Province in 2021
- Sichuan Medical Association [S21037]
- Medical Research Project of Chengdu Municipal Health Commission [2022113]
Supplementation of 25(OH)D-3 has metabolic advantages over 1,25(OH)(2)D-3 supplementation in improving muscle atrophy and fat browning.
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 mu g/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.
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