饮食中磷对男性和女性C末端及完整成纤维细胞生长因子23（FGF-23）的调节作用

Regulation of C-terminal and intact FGF-23 by dietary phosphate in men and women.

作者信息

Burnett Sherri -Ann M, Gunawardene Samantha C, Bringhurst F Richard, Jüppner Harald, Lee Hang, Finkelstein Joel S

机构信息

Endocrine Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.

出版信息

J Bone Miner Res. 2006 Aug;21(8):1187-96. doi: 10.1359/jbmr.060507.

DOI:10.1359/jbmr.060507

PMID:16869716

Abstract

UNLABELLED

FGF-23 is a novel regulator of phosphate metabolism. We studied the regulation of FGF-23 by dietary phosphate in 66 men and women using two assays. Dietary phosphate restriction decreased FGF-23 and loading increased FGF-23 significantly. An assay that measured intact FGF-23 showed the effects of dietary phosphate much more clearly than an assay that also measures presumed biologically inactive fragments. Dietary phosphate is a key regulator of circulating FGF-23; choice of assay is critical when studying FGF-23 physiology.

INTRODUCTION

Fibroblast growth factor 23 (FGF-23) is a novel phosphaturic factor discovered through genetic studies of patients with renal phosphate wasting disorders. Ablation of the FGF-23 gene in mice reduces renal phosphate excretion and increases serum phosphate, suggesting that FGF-23 is critical for normal phosphate homeostasis. We examined the role of dietary phosphate in the regulation of FGF-23 in humans.

MATERIALS AND METHODS

Sixty-six healthy males and females were randomized to either phosphate-depleted or -loaded diets for 5 days, after a 4-day run-in diet. FGF-23 was measured using an "intact" assay that only detects intact FGF-23 peptide and with a "C-terminal" assay that measures both intact FGF-23 peptide and presumed biologically inactive carboxyl terminal fragments. The main outcome was the within group change in FGF-23 with either phosphate depletion or loading.

RESULTS

Using the intact FGF-23 assay, mean FGF-23 area under the curve (AUC) decreased by 9 +/- 16% with phosphate depletion (p = 0.0041) and increased by 35 +/- 29% with loading (p < 0.0001). Using the C-terminal FGF-23 assay, mean FGF-23 AUC decreased by 8 +/- 12% with phosphate depletion (p = 0.0003) and increased by 13 +/- 20% with loading (p = 0.0016). Increases in FGF-23 with phosphate loading were greater with the intact assay than with the C-terminal assay (p = 0.0003). Using the intact assay only, FGF-23 was significantly associated with serum phosphate (r = 0.39, p < 0.01), 24-h urinary phosphate (r = 0.47, p < 0.01), fractional excretion of phosphate (r = 0.29, p < 0.01), and 1,25-dihydroxyvitamin D (r = -0.30, p < 0.01). The association between the assays was weak (r = 0.26, p < 0.01).

CONCLUSIONS

Dietary phosphate is a key regulator of circulating FGF-23 levels in humans. Additionally, choice of assay is critical when performing physiologic investigations of FGF-23.

摘要

未标注

成纤维细胞生长因子23（FGF - 23）是磷酸盐代谢的一种新型调节因子。我们通过两种检测方法研究了66名男性和女性饮食中磷酸盐对FGF - 23的调节作用。饮食中磷酸盐限制会降低FGF - 23水平，而磷酸盐负荷增加则会显著提高FGF - 23水平。一种检测完整FGF - 23的方法比另一种同时检测假定无生物活性片段的方法更能清晰地显示饮食中磷酸盐的作用。饮食中的磷酸盐是循环FGF - 23的关键调节因子；在研究FGF - 23生理学特性时，检测方法的选择至关重要。

引言

成纤维细胞生长因子23（FGF - 23）是通过对患有肾性磷酸盐消耗性疾病患者的基因研究发现的一种新型促尿磷排泄因子。小鼠体内FGF - 23基因的缺失会减少肾脏磷酸盐排泄并增加血清磷酸盐水平，这表明FGF - 23对正常磷酸盐稳态至关重要。我们研究了饮食中磷酸盐在人体对FGF - 23调节中的作用。

材料与方法

66名健康男性和女性在经过4天的适应期饮食后，被随机分为低磷饮食组或高磷饮食组，为期5天。使用一种仅检测完整FGF - 23肽的“完整”检测方法以及一种同时检测完整FGF - 23肽和假定无生物活性的羧基末端片段的“C末端”检测方法来测量FGF - 23。主要观察指标是低磷或高磷饮食组内FGF - 23的变化。

结果

使用完整FGF - 23检测方法，低磷饮食时FGF - 23曲线下面积（AUC）平均降低9±16%（p = 0.0041），高磷饮食时增加35±29%（p < 0.0001）。使用C末端FGF - 23检测方法，低磷饮食时FGF - 23 AUC平均降低8±12%（p = 0.0003），高磷饮食时增加13±20%（p = 0.0016）。完整检测方法显示高磷饮食时FGF - 23的增加幅度大于C末端检测方法（p = 0.0003）。仅使用完整检测方法时，FGF - 23与血清磷酸盐（r = 0.39，p < 0.01）、24小时尿磷酸盐（r = 0.47，p < 0.01）、磷酸盐排泄分数（r = 0.29，p < 0.01）以及1,25 - 二羟基维生素D（r = -0.30，p < 0.01）显著相关。两种检测方法之间的相关性较弱（r = 0.26，p < 0.01）。