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Submitted on June 28, 2005
Accepted on August 18, 2005
Pediatrics, University of California San Francisco, San Francisco, California, United States; Pediatrics, University of Texas Medical Branch, Galveston, Texas, United States; Pharmaceutical Research Laboratories, Kirin Brewery Co. Ltd., Takasaki, Gunma, Japan; Pediatrics and Human Genetics, McGill University, Montreal, Quebec, Canada
* To whom correspondence should be addressed. E-mail: aportale{at}peds.ucsf.edu.
Fibroblast growth factor-23 (FGF-23) is a novel circulating peptide that regulates phosphate (
) and vitamin D metabolism, but the mechanisms by which circulating FGF-23 itself is regulated are unknown. To determine whether serum FGF-23 concentration is regulated by dietary intake of , we fed wild-type (WT), Npt2a gene-ablated (Npt2a-) and Hyp mice diets containing varying content (0.02 to 1.65%). In WT mice, increases in dietary intake from 0.02% to 1.65% induced a 7-fold increase in serum FGF-23 and a 3-fold increase in serum concentrations. Across the range of dietary , serum FGF-23 concentrations varied directly with serum concentrations (R2=0.72, P < 0.001). In Npt2a- mice, serum FGF-23 concentrations were significantly lower than in WT mice, and these differences could be accounted for by the lower serum levels in Npt2a- mice. The serum concentrations of FGF-23 in Hyp mice were 5-fold to 25-fold higher than values in wild-type mice, and the values varied directly with dietary intake. Fgf-23 mRNA abundance in calvaria was significantly higher in Hyp mice than in WT mice on the 1% diet; and in both groups of mice, fgf-23 mRNA abundance in calvarial bone was suppressed by 85% on the low (0.02%) diet. In WT mice fed the low (0.02%) diet, renal 1
-hydroxylase activity and P450c1 mRNA abundance were significantly higher than values in mice fed the higher diets and varied inversely with serum FGF-23 concentrations (R2 = 0.86 and R2 = 0.64, P < 0.001, respectively). The present data demonstrate that dietary regulates serum FGF-23 concentration in mice, and that such regulation is independent of phex function. The data suggest that genotype-dependent and dietary -induced changes in serum FGF-23 concentration reflect changes in fgf-23 gene expression in bone.
-hydroxylase •
1,25(OH)2D •
phosphorus •
Npt2 •
Hyp
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