Exercise-stimulated FGF23 promotes exercise performance via controlling the excess reactive oxygen species production and enhancing mitochondrial function in skeletal muscle
Exercise-stimulated FGF23 promotes exercise performance via controlling the excess reactive oxygen species production and enhancing mitochondrial function in skeletal muscle
复制标题
运动刺激的 FGF23 通过控制过量活性氧的产生和增强骨骼肌中的线粒体功能来促进运动表现。
DOI：
10.1016/j.metabol.2016.02.009
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发表时间：
2016-05-01
影响因子：
9.8
通讯作者：
Shen, Fu-Ming
中科院分区：
文献类型：
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作者：
Li, Dong-Jie;Fu, Hui;Shen, Fu-Ming
目标。体育锻炼能诱导骨骼肌和全身的许多适应性变化，改善代谢特征。成纤维细胞生长因子23(FGF23)是成纤维细胞生长因子家族中一个独特的成员，它作为一种激素调节磷酸盐代谢、骨化三醇浓度和肾功能。FGF23在运动和骨骼肌中的作用在很大程度上还不清楚。C57BL/6J小鼠在运动跑步机上锻炼。分别采用单次急性运动(60min)、力竭运动(每天60min)和慢性长时间运动(每天60min，持续1周)，采用酶联免疫吸附试验、实时聚合酶链式反应和免疫印迹法检测小鼠血清FGF23水平、肝脏、心脏、骨骼肌组织和甲状腺组织中FGF23mRNA的表达以及FGF23受体Klotho的表达。给C57BL/6J小鼠腹腔注射重组FGF23(100 mg/kg，2次/d)。检测大鼠运动能力、肌肉中活性氧(ROS)、过氧化氢(H_2O_2)生成量、肌肉线粒体功能生物标志物(sirtuin 1、PPAR-Delta、PGC-1α和线粒体转录因子A[TFAM]的基因表达及柠檬酸合酶活性)。急性运动、力竭运动和慢性运动三种形式的运动均使血清FGF23水平升高。然而，只有慢性运动上调了骨骼肌中FGF23mRNA和蛋白的表达。心脏、肝脏和甲状腺组织中FGF23mRNA的表达未受影响。FGF23蛋白主要定位于骨骼肌组织的胞浆中，运动对FGF23的定位无明显影响。外源性FGF23处理可显著延长小鼠的力竭时间，减少运动诱导的ROS和H_2O_2的产生。FGF23治疗可提高骨骼肌中PPAR-Delta的mRNA水平和柠檬酸合酶活性，但不影响sirtuin 1、PGC-1α和TFAM的mRNA表达。这些结果表明，运动刺激的FGF23通过控制骨骼肌中过量的ROS产生和增强线粒体功能来促进运动成绩，这揭示了FGF23在骨骼肌中的一个全新的作用。(C)2016 Elsevier Inc.保留所有权利。
Objective. Physical exercise induces many adaptive changes in skeletal muscle and the whole body and improves metabolic characteristics. Fibroblast growth-factor 23 (FGF23) is a unique member of the FGF family that acts as a hormone regulating phosphate metabolism, calcitriol concentration, and kidney functions. The role of FGF23 in exercise and skeletal muscle is largely unknown yetMaterials and methods. C57BL/6J mice were exercised on a motor treadmill. Mice serum FGF23 levels; FGF23 mRNA expression in various organs including the liver, heart, skeletal muscle tissue, and thyroid; and FGF23 receptor Klotho mRNA expression were examined using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and immunoblotting, respectively, after a single bout of acute exercise (60 min), exhaustive exercise, and chronic prolonged exercise (60 min every day for one week). C57BL/6J mice were injected with recombinant FGF23 (100 mg/kg, twice per day, i.p.) or vehicle control (saline) for 3 days, and then the exercise performance, reactive oxygen species (ROS), H2O2 production, and mitochondrial functional biomarkers in muscle (gene expression of sirtuin 1, PPAR-delta, PGC-1 alpha and mitochondrial transcription factor A [TFAM], and citrate synthase activity) were assayed.Results. Three forms of exercise, acute exercise, exhaustive exercise, and chronic exercise, increased serum FGF23 levels. However, only chronic exercise upregulated FGF23 mRNA and protein expression in skeletal muscle. FGF23 mRNA expression in the heart, liver, and thyroid was not affected. FGF23 protein was mainly located in the cytoplasm in skeletal muscle tissue and the localization of FGF23 was not altered by exercise. Exogenous FGF23 treatment significantly extended the time to exhaustion and reduced the exercise-induced ROS and H2O2 production. FGF23 treatment increased the mRNA level of PPAR-delta and citrate synthase activity, but did not influence the mRNA expression of sirtuin 1, PGC-1 alpha, and TFAM in skeletal muscle.Conclusion. These results demonstrate that exercise-stimulated FGF23 promotes exercise performance via controlling the excess ROS production and enhancing mitochondrial function in skeletal muscle, which reveals an entirely novel role of FGF23 in skeletal muscle. (C) 2016 Elsevier Inc. All rights reserved.