{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T16:08:20Z","timestamp":1779206900634,"version":"3.51.4"},"reference-count":42,"publisher":"The Endocrine Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,4,1]]},"abstract":"<jats:p>It is still controversial whether the bone-derived hormone fibroblast growth factor-23 (FGF23) has additional physiological functions apart from its well-known suppressive actions on renal phosphate reabsorption and vitamin D hormone synthesis. Here we analyzed premature aging, mineral homeostasis, carbohydrate metabolism, and fat metabolism in 9-month-old male wild-type (WT) mice, vitamin D receptor mutant mice (VDR\u0394\/\u0394) with a nonfunctioning vitamin D receptor, and Fgf23\u2212\/\u2212\/VDR\u0394\/\u0394 compound mutant mice on both a standard rodent chow and a rescue diet enriched with calcium, phosphorus, and lactose. Organ atrophy, lung emphysema, and ectopic tissue or vascular calcifications were absent in compound mutants. In addition, body weight, glucose tolerance, insulin tolerance, insulin secretory capacity, pancreatic beta cell volume, and retroperitoneal and epididymal fat mass as well as serum cholesterol and triglycerides were indistinguishable between vitamin D receptor and compound mutants. In contrast to VDR\u0394\/\u0394 and Fgf23\u2212\/\u2212\/VDR\u0394\/\u0394 mice, which stayed lean, WT mice showed obesity-induced insulin resistance. To rule out alopecia and concomitantly elevated energy expenditure present in 9-month-old VDR\u0394\/\u0394 and Fgf23\u2212\/\u2212\/VDR\u0394\/\u0394 mice as a confounding factor for the lacking effect of Fgf23 deficiency on fat mass, we analyzed whole-body composition in WT, Fgf23\u2212\/\u2212, VDR\u0394\/\u0394, and Fgf23\u2212\/\u2212\/VDR\u0394\/\u0394 mice at the age of 4 wk, when the coat in VDR\u0394\/\u0394 mice is still normal. Whole-body fat mass was reduced in Fgf23\u2212\/\u2212 mice but almost identical in WT, VDR\u0394\/\u0394, and Fgf23\u2212\/\u2212\/VDR\u0394\/\u0394 mice. In conclusion, our data indicate that Fgf23 has no molecular vitamin D-independent role in aging, insulin signaling, or fat metabolism in mice.<\/jats:p>","DOI":"10.1210\/en.2011-1878","type":"journal-article","created":{"date-parts":[[2012,2,1]],"date-time":"2012-02-01T03:12:20Z","timestamp":1328065940000},"page":"1795-1805","source":"Crossref","is-referenced-by-count":50,"title":["Long-Term Fgf23 Deficiency Does Not Influence Aging, Glucose Homeostasis, or Fat Metabolism in Mice with a Nonfunctioning Vitamin D Receptor"],"prefix":"10.1210","volume":"153","author":[{"given":"Carmen","family":"Streicher","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences (C.S., U.Z., O.A., A.R., E.P., R.G.E.), University of Veterinary Medicine, 1210 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ute","family":"Zeitz","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences (C.S., U.Z., O.A., A.R., E.P., R.G.E.), University of Veterinary Medicine, 1210 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olena","family":"Andrukhova","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences (C.S., U.Z., O.A., A.R., E.P., R.G.E.), University of Veterinary Medicine, 1210 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Rupprecht","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences (C.S., U.Z., O.A., A.R., E.P., R.G.E.), University of Veterinary Medicine, 1210 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Pohl","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences (C.S., U.Z., O.A., A.R., E.P., R.G.E.), University of Veterinary Medicine, 1210 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias E.","family":"Larsson","sequence":"first","affiliation":[{"name":"Department of Medical Sciences (T.E.L.), Uppsala University, 751 85 Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wilhelm","family":"Windisch","sequence":"first","affiliation":[{"name":"Department of Food Science and Technology (W.W.), University of Applied Life Sciences, 1180 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beate","family":"Lanske","sequence":"first","affiliation":[{"name":"Department of Developmental Biology (B.L.), Harvard School of Dental Medicine, Boston, Massachusetts 02215"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reinhold G.","family":"Erben","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences (C.S., U.Z., O.A., A.R., E.P., R.G.E.), University of Veterinary Medicine, 1210 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2012,1,31]]},"reference":[{"key":"2020071612435932700_B1","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/81664","article-title":"Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23.","volume":"26","author":"The ADHR Consortium","year":"2000","journal-title":"Nat Genet"},{"key":"2020071612435932700_B2","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1046\/j.1523-1755.2001.00064.x","article-title":"Autosomal-dominant hypophosphatemic rickets (ADHR) mutations stabilize FGF-23.","volume":"60","author":"White","year":"2001","journal-title":"Kidney Int"},{"key":"2020071612435932700_B3","doi-asserted-by":"crossref","first-page":"3179","DOI":"10.1210\/endo.143.8.8795","article-title":"Mutant FGF-23 responsible for autosomal dominant hypophosphatemic rickets is resistant to proteolytic cleavage and causes hypophosphatemia in 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osteomalacia.","volume":"98","author":"Shimada","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071612435932700_B7","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1359\/JBMR.0301264","article-title":"FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis.","volume":"19","author":"Shimada","year":"2004","journal-title":"J Bone Miner Res"},{"key":"2020071612435932700_B8","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.bbrc.2003.12.102","article-title":"FGF-23 transgenic mice demonstrate hypophosphatemic rickets with reduced expression of sodium phosphate cotransporter type IIa.","volume":"314","author":"Shimada","year":"2004","journal-title":"Biochem Biophys Res Commun"},{"key":"2020071612435932700_B9","doi-asserted-by":"crossref","first-page":"3087","DOI":"10.1210\/en.2003-1768","article-title":"Transgenic mice expressing fibroblast growth factor 23 under the control of the \u03b11(I) collagen promoter exhibit 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FGF23.","volume":"444","author":"Urakawa","year":"2006","journal-title":"Nature"},{"key":"2020071612435932700_B13","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/36285","article-title":"Mutation of the mouse klotho gene leads to a syndrome resembling ageing.","volume":"390","author":"Kuro-o","year":"1997","journal-title":"Nature"},{"key":"2020071612435932700_B14","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.bbagen.2009.02.005","article-title":"Klotho and aging.","volume":"1790","author":"Kuro-o","year":"2009","journal-title":"Biochim Biophys Acta"},{"key":"2020071612435932700_B15","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1172\/JCI200419081","article-title":"Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism.","volume":"113","author":"Shimada","year":"2004","journal-title":"J Clin 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