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Long-Term Fgf23 Deficiency Does Not Influence Aging, Glucose Homeostasis, or Fat Metabolism in Mice with a Nonfunctioning Vitamin D Receptor
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2012 (English)In: Endocrinology, ISSN 0013-7227, E-ISSN 1945-7170, Vol. 153, no 4, 1795-1805 p.Article in journal (Refereed) Published
Abstract [en]

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 wildtype (WT) mice, vitamin D receptor mutant mice (VDR Delta/Delta) with a nonfunctioning vitamin D receptor, and Fgf23(-/-)/VDR Delta/Delta 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 Delta/Delta and Fgf23(-/-)/VDR Delta/Delta 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 Delta/Delta and Fgf23(-/-)/VDR Delta/Delta mice as a confounding factor for the lacking effect of Fgf23 deficiency on fat mass, we analyzed whole-body composition in WT, Fgf23(-/-), VDR Delta/Delta, and Fgf23(-/-)/VDR Delta/Delta mice at the age of 4 wk, when the coat in VDR Delta/Delta mice is still normal. Whole-body fat mass was reduced in Fgf23(-/-) mice but almost identical in WT, VDR Delta/Delta, and Fgf23(-/-)/VDR Delta/Delta mice. In conclusion, our data indicate that Fgf23 has no molecular vitamin D-independent role in aging, insulin signaling, or fat metabolism in mice. 

Place, publisher, year, edition, pages
2012. Vol. 153, no 4, 1795-1805 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-173652DOI: 10.1210/en.2011-1878ISI: 000302169800028OAI: oai:DiVA.org:uu-173652DiVA: diva2:524483
Available from: 2012-05-02 Created: 2012-05-02 Last updated: 2012-05-02Bibliographically approved

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Larsson, Tobias E.
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