title: Long-term Fgf23 deficiency does not influence aging, glucose homeostasis, or fat metabolism in mice with a nonfunctioning vitamin D receptor.
abstract: 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(Δ/Δ)) with a nonfunctioning vitamin D receptor, and Fgf23⁻/⁻/VDR(Δ/Δ) 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(Δ/Δ) and Fgf23⁻/⁻/VDR(Δ/Δ) 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(Δ/Δ) and Fgf23⁻/⁻/VDR(Δ/Δ) mice as a confounding factor for the lacking effect of Fgf23 deficiency on fat mass, we analyzed whole-body composition in WT, Fgf23⁻/⁻, VDR(Δ/Δ), and Fgf23⁻/⁻/VDR(Δ/Δ) mice at the age of 4 wk, when the coat in VDR(Δ/Δ) mice is still normal. Whole-body fat mass was reduced in Fgf23⁻/⁻ mice but almost identical in WT, VDR(Δ/Δ), and Fgf23⁻/⁻/VDR(Δ/Δ) mice. In conclusion, our data indicate that Fgf23 has no molecular vitamin D-independent role in aging, insulin signaling, or fat metabolism in mice.
authors.affiliation: Department of Biomedical Sciences, University of Veterinary Medicine, 1210 Vienna, Austria.
authors.forename: Carmen
authors.initials: C
authors.lastname: Streicher
authors.forename: Ute
authors.initials: U
authors.lastname: Zeitz
authors.forename: Olena
authors.initials: O
authors.lastname: Andrukhova
authors.forename: Anne
authors.initials: A
authors.lastname: Rupprecht
authors.forename: Elena
authors.initials: E
authors.lastname: Pohl
authors.forename: Tobias E
authors.initials: TE
authors.lastname: Larsson
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Windisch
authors.forename: Beate
authors.initials: B
authors.lastname: Lanske
authors.forename: Reinhold G
authors.initials: RG
authors.lastname: Erben
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000172:deficiency* / Q000235:genetics; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D007328:Insulin / Q000502:physiology; D050356:Lipid Metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D023421:Models, Animal; D009154:Mutation / Q000235:genetics; D018167:Receptors, Calcitriol / Q000172:deficiency* / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D014807:Vitamin D / Q000502:physiology
chemical_list: C000717428:Fgf23 protein, mouse; D007328:Insulin; D018167:Receptors, Calcitriol; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005947:Glucose