This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Perwad, F. Articles by Portale, A. A. Search for Related Content PubMed PubMed Citation Articles by Perwad, F. Articles by Portale, A. A.

Dietary and Serum Phosphorus Regulate Fibroblast Growth Factor 23 Expression and 1,25-Dihydroxyvitamin D Metabolism in Mice

Department of Pediatrics, University of California (F.P., M.Y.H.Z., A.A.P.), San Francisco, California 94143-0748; Department of Pediatrics, University of Texas Medical Branch (N.A.), Galveston, Texas 77555; Pharmaceutical Research Laboratories, Kirin Brewery Co. Ltd. (T.Y.), Takasaki, Gunma 370-1295, Japan; and Department of Pediatrics and Human Genetics, McGill University (H.S.T.), Montréal, Québec, Canada H3Z 2Z3

Address all correspondence and requests for reprints to: Dr. Anthony A. Portale, 533 Parnassus Avenue, Room U-585, University of California, San Francisco, California 94143-0748. E-mail: aportale{at}peds.ucsf.edu.

Fibroblast growth factor-23 (FGF-23) is a novel circulating peptide that regulates phosphorus (Pi) and vitamin D metabolism, but the mechanisms by which circulating FGF-23 itself is regulated are unknown. To determine whether the serum FGF-23 concentration is regulated by dietary intake of Pi, we fed wild-type (WT), Npt2a gene-ablated (Npt2a^–/–), and Hyp mice diets containing varying Pi contents (0.02–1.65%). In WT mice, increases in dietary Pi intake from 0.02–1.65% induced a 7-fold increase in serum FGF-23 and a 3-fold increase in serum Pi concentrations. Across the range of dietary Pi, serum FGF-23 concentrations varied directly with serum Pi 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 Pi levels in Npt2a^–/– mice. The serum concentrations of FGF-23 in Hyp mice were 5- to 25-fold higher than values in WT mice, and the values varied with dietary Pi intake. Fgf-23 mRNA abundance in calvaria was significantly higher in Hyp mice than in WT mice on the 1% Pi diet; in both groups of mice, fgf-23 mRNA abundance in calvarial bone was suppressed by 85% on the low (0.02%) Pi diet. In WT mice fed the low (0.02%) Pi diet, renal mitochondrial 1-hydroxylase activity and renal 1-hydroxylase (P450c1) mRNA abundance were significantly higher than in mice fed the higher Pi 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 Pi regulates the serum FGF-23 concentration in mice, and such regulation is independent of phex function. The data suggest that genotype-dependent and dietary Pi-induced changes in the serum FGF-23 concentration reflect changes in fgf-23 gene expression in bone.

This article has been cited by other articles:

				W. W. Brown, H. Juppner, C. B. Langman, H. Price, E. G. Farrow, K. E. White, and K. L. McCormick Hypophosphatemia with Elevations in Serum Fibroblast Growth Factor 23 in a Child with Jansen's Metaphyseal Chondrodysplasia J. Clin. Endocrinol. Metab., January 1, 2009; 94(1): 17 - 20. [Abstract] [Full Text] [PDF]

				U. S. Alon, R. Levy-Olomucki, W. V. Moore, J. Stubbs, S. Liu, and L. D. Quarles Calcimimetics as an Adjuvant Treatment for Familial Hypophosphatemic Rickets Clin. J. Am. Soc. Nephrol., May 1, 2008; 3(3): 658 - 664. [Abstract] [Full Text] [PDF]

				L. Thomas and R. Kumar Control of Renal Solute Excretion by Enteric Signals and Mediators J. Am. Soc. Nephrol., February 1, 2008; 19(2): 207 - 212. [Abstract] [Full Text] [PDF]

				R. Marsell, E. Grundberg, T. Krajisnik, H. Mallmin, M. Karlsson, D. Mellstrom, E. Orwoll, C. Ohlsson, K. B Jonsson, O. Ljunggren, et al. Fibroblast growth factor-23 is associated with parathyroid hormone and renal function in a population-based cohort of elderly men Eur. J. Endocrinol., January 1, 2008; 158(1): 125 - 129. [Abstract] [Full Text] [PDF]

				F. Perwad, M. Y. H. Zhang, H. S. Tenenhouse, and A. A. Portale Fibroblast growth factor 23 impairs phosphorus and vitamin D metabolism in vivo and suppresses 25-hydroxyvitamin D-1{alpha}-hydroxylase expression in vitro Am J Physiol Renal Physiol, November 1, 2007; 293(5): F1577 - F1583. [Abstract] [Full Text] [PDF]

				T. Kawata, Y. Imanishi, K. Kobayashi, T. Miki, A. Arnold, M. Inaba, and Y. Nishizawa Parathyroid Hormone Regulates Fibroblast Growth Factor-23 in a Mouse Model of Primary Hyperparathyroidism J. Am. Soc. Nephrol., October 1, 2007; 18(10): 2683 - 2688. [Abstract] [Full Text] [PDF]

				T. Berndt, L. F. Thomas, T. A. Craig, S. Sommer, X. Li, E. J. Bergstralh, and R. Kumar Evidence for a signaling axis by which intestinal phosphate rapidly modulates renal phosphate reabsorption PNAS, June 26, 2007; 104(26): 11085 - 11090. [Abstract] [Full Text] [PDF]

				S. Liu and L. D. Quarles How Fibroblast Growth Factor 23 Works J. Am. Soc. Nephrol., June 1, 2007; 18(6): 1637 - 1647. [Abstract] [Full Text] [PDF]

				K. J. Martin and E. A. Gonzalez Metabolic Bone Disease in Chronic Kidney Disease J. Am. Soc. Nephrol., March 1, 2007; 18(3): 875 - 885. [Abstract] [Full Text] [PDF]

				D. M. Antoniucci, T. Yamashita, and A. A. Portale Dietary Phosphorus Regulates Serum Fibroblast Growth Factor-23 Concentrations in Healthy Men J. Clin. Endocrinol. Metab., August 1, 2006; 91(8): 3144 - 3149. [Abstract] [Full Text] [PDF]

				S. Liu, W. Tang, J. Zhou, J. R. Stubbs, Q. Luo, M. Pi, and L. D. Quarles Fibroblast Growth Factor 23 Is a Counter-Regulatory Phosphaturic Hormone for Vitamin D J. Am. Soc. Nephrol., May 1, 2006; 17(5): 1305 - 1315. [Abstract] [Full Text] [PDF]