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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 \u03bcg\/kg\/day) or 1,25(OH)2D3 (60 ng\/kg\/day) resulted in Ctns\u2212\/\u2212 mice corrected low circulating 25(OH)D3 or 1,25(OH)2D3 concentrations. While 25(OH)D3 administration in Ctns\u2212\/\u2212 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\u2212\/\u2212 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\u2212\/\u2212 mice.<\/jats:p>","DOI":"10.3390\/cells11203264","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T21:11:51Z","timestamp":1666041111000},"page":"3264","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Metabolic Advantage of 25(OH)D3 versus 1,25(OH)2D3 Supplementation in Infantile Nephropathic Cystinosis-Associated Adipose Tissue Browning and Muscle Wasting"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9680-1651","authenticated-orcid":false,"given":"Ping","family":"Zhou","sequence":"first","affiliation":[{"name":"Division of Pediatric Nephrology, Rady Children\u2019s Hospital, University of California, San Diego, CA 92093, USA"},{"name":"Department of Pediatric Nephrology and Rheumatology, Sichuan Provincial Maternity and Child Health Care Hospital and The Affiliated Women\u2019s and Children\u2019s Hospital of Chengdu Medical College, Chengdu 610031, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wai W.","family":"Cheung","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology, Rady Children\u2019s Hospital, University of California, San Diego, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology, Rady Children\u2019s Hospital, University of California, San Diego, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Venya","family":"Vaddi","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology, Rady Children\u2019s Hospital, University of California, San Diego, CA 92093, USA"},{"name":"Integrative Biology & Physiology, University of California, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo A.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology, Rady Children\u2019s Hospital, University of California, San Diego, CA 92093, USA"},{"name":"Department of Pediatrics, Health Sciences Postgraduate Program, School of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte 30310-100, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert H.","family":"Mak","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology, Rady Children\u2019s Hospital, University of California, San Diego, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/ng0498-319","article-title":"A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis","volume":"18","author":"Town","year":"1998","journal-title":"Nat. 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