Dietary and serum phosphorus regulate fibroblast growth factor 23 expression and 1,25-dihydroxyvitamin D metabolism in mice

Endocrinology. 2005 Dec;146(12):5358-64. doi: 10.1210/en.2005-0777. Epub 2005 Aug 25.

Abstract

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 (r(2) = 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 1alpha-hydroxylase activity and renal 1alpha-hydroxylase (P450c1alpha) mRNA abundance were significantly higher than in mice fed the higher Pi diets and varied inversely with serum FGF-23 concentrations (r(2) = 0.86 and r(2) = 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone and Bones / metabolism
  • Fibroblast Growth Factors / blood
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism*
  • Hypophosphatemia, Familial / blood
  • Kidney / enzymology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Osmolar Concentration
  • Phosphorus / blood*
  • Phosphorus, Dietary / pharmacology*
  • RNA, Messenger / metabolism
  • Sodium-Phosphate Cotransporter Proteins, Type IIa / deficiency
  • Steroid Hydroxylases / genetics
  • Steroid Hydroxylases / metabolism
  • Vitamin D / analogs & derivatives*
  • Vitamin D / metabolism
  • Vitamin D3 24-Hydroxylase

Substances

  • Phosphorus, Dietary
  • RNA, Messenger
  • Sodium-Phosphate Cotransporter Proteins, Type IIa
  • Vitamin D
  • Phosphorus
  • Fibroblast Growth Factors
  • 1,25-dihydroxyvitamin D
  • fibroblast growth factor 23
  • Steroid Hydroxylases
  • vitamin D 1-alpha hydroxylase
  • Vitamin D3 24-Hydroxylase