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: Carmen Streicher, Ute Zeitz, Olena Andrukhova, Anne Rupprecht, Elena Pohl, Tobias E Larsson, Wilhelm Windisch, Beate Lanske, Reinhold G Erben
• Journal: Endocrinology (Endocrinology) Vol. 153 Issue 4 Pg. 1795-805 (Apr 2012) ISSN: 1945-7170 [Electronic] United States
• PMID: 22294750 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Fgf23 protein, mouse
• Insulin
• Receptors, Calcitriol
• Vitamin D
• Fibroblast Growth Factors
• Fibroblast Growth Factor-23
• Glucose

Topics

• Aging (physiology)
• Animals
• Fibroblast Growth Factor-23
• Fibroblast Growth Factors (deficiency, genetics)
• Glucose (metabolism)
• Homeostasis (physiology)
• Insulin (physiology)
• Lipid Metabolism (physiology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Mutant Strains
• Models, Animal
• Mutation (genetics)
• Receptors, Calcitriol (deficiency, genetics)
• Signal Transduction (physiology)
• Vitamin D (physiology)