Dietary and serum phosphorus regulate fibroblast growth factor 23 expression and 1,25-dihydroxyvitamin D metabolism in mice
Dietary and serum phosphorus regulate fibroblast growth factor 23 expression and 1,25-dihydroxyvitamin D metabolism in mice
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DOI：
10.1210/en.2005-0777
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发表时间：
2005-12-01
期刊：
影响因子：
4.8
通讯作者：
Portale, AA
中科院分区：
文献类型：
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作者：
Perwad, F;Azam, N;Portale, AA
成纤维细胞生长因子-23 （FGF-23）是一种调节磷（Pi）和维生素D代谢的新型循环肽，但循环FGF-23本身的调节机制尚不清楚。为了确定血清FGF-23浓度是否受膳食摄入Pi的调节，我们给野生型（WT）、Npt2a基因消融（Npt2a(-/-)）和Hyp小鼠喂食含有不同Pi含量（0.02-1.65%）的饲料。在WT小鼠中，膳食Pi摄入量从0.02-1.65%增加可导致血清FGF-23增加7倍，血清Pi浓度增加3倍。在饲粮Pi范围内，血清FGF-23浓度与血清Pi浓度直接变化(r(2) = 0.72；P < 0.001)。在Npt2a（-/-）小鼠中，血清FGF-23浓度显著低于WT小鼠，这些差异可能是由于Npt2a（-/-）小鼠的血清Pi水平较低。Hyp小鼠血清中FGF-23的浓度比WT小鼠高5- 25倍，且随膳食Pi摄入量的变化而变化。高脂小鼠颅骨中Fgf-23 mRNA的丰度显著高于低脂小鼠；在两组小鼠中，低（0.02%）Pi饮食抑制了颅骨中fgf-23 mRNA丰度85%。低（0.02%）Pi饲粮的WT小鼠肾脏线粒体1 α -羟化酶活性和肾脏1 α -羟化酶（P450c1 α） mRNA丰度显著高于高Pi饲粮的小鼠，且与血清FGF-23浓度呈负相关(r(2) = 0.86和r(2) = 0.64；P < 0.001)。目前的数据表明，膳食Pi调节小鼠血清FGF-23浓度，这种调节是独立于phex功能的。这些数据表明，基因型依赖性和膳食pi诱导的血清FGF-23浓度变化反映了骨中FGF-23基因表达的变化。
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 1 alpha-hydroxylase activity and renal 1 alpha-hydroxylase (P450c1 alpha) 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.