TY - JOUR
T1 - Long-term Fgf23 deficiency does not influence aging, glucose homeostasis, or fat metabolism in mice with a nonfunctioning vitamin D receptor
AU - Streicher, Carmen
AU - Zeitz, Ute
AU - Andrukhova, Olena
AU - Rupprecht, Anne
AU - Pohl, Elena
AU - Larsson, Tobias E.
AU - Windisch, Wilhelm
AU - Lanske, Beate
AU - Erben, Reinhold G.
PY - 2012/4
Y1 - 2012/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84859384642&partnerID=8YFLogxK
U2 - 10.1210/en.2011-1878
DO - 10.1210/en.2011-1878
M3 - Article
C2 - 22294750
AN - SCOPUS:84859384642
SN - 0013-7227
VL - 153
SP - 1795
EP - 1805
JO - Endocrinology
JF - Endocrinology
IS - 4
ER -