FGF23 تحریک شده با ورزش کارایی ورزش را توسط کنترل تولید اضافی گونه های فعال اکسیژن و افزایش عملکرد میتوکندریایی در عضله اسکلتی ارتقا می دهد Exercise-stimulated FGF23 promotes exercise performance via controlling the excess reactive oxygen species production and enhancing mitochondrial function in skeletal muscle

۱٫ Introduction Over the last 30 years, the combination of both a sedentary lifestyle and excessive food availability has led to a significant increase in the prevalence of obesity and aggravation of rates of type 2 diabetes mellitus. Physical exercise is one of the most effective therapeutic strategies for metabolic disorders [1]. Exercise induces many physiological changes, including improving metabolic status, enhancing insulin sensitivity, and reducing risk of cardiovascular disease [2-5]. However, physical exercise may induce excess reactive oxygen species (ROS) in skeletal muscle, which may lead to muscle damage [6]. Thus, understanding the exercise-induced intramuscular and whole-body responsive adaptations is beneficial for alleviating the unfavorable effects of exercise, and it may help to develop new and more effective means in combating metabolic and cardiovascular disorders. Fibroblast growth factors (FGFs) are a large family of secreted factors composed of at least 23 members, some of which exist in different isoforms. They are structurally related and characterized by high affinity to heparin[7]. FGFs play critical roles in regulation of metabolism and endocrine function [8-10]. FGF23 was identified as the last member of the FGF family. FGF23 is a unique member of the FGF family because it acts as a hormone that derives from bone[11]. Circulating FGF23 regulates serum phosphorus, calcitriol concentration, and kidney functions, whereas most other FGF family members are thought to regulate various cell functions at a local level[11]. Gene knockout of FGF23 in mice induces aging-like features, including shortened life span, growth retardation, hypogonadism, cognition impairment, hearing loss, vascular calcification, and cardiac hypertrophy[11]. Further, FGF23 has been found to be a potential biomarker in cardiovascular and renal diseases, besides its role in phosphate homeostasis and bone biology. High blood FGF23 level is associated with chronic kidney diseases [12] and coronary artery disease [13]. Moreover, FGF23 increases distal renal tubular Na+ uptake and leads to volume expansion [14], and underlies some metabolic action of leptin [15]. Nevertheless, the role of FGF23 in skeletal muscle was rarely investigated, although previous studies have shown the expression of FGF23 in skeletal muscle tissue [16]. Thus, we speculated that FGF23 might play an important role in skeletal muscle. In the present study, we examined the effects of three forms of physical exercise on serum FGF23 concentrations and FGF23 expression in skeletal muscle in mice. Moreover, we evaluated the effects of FGF23 treatment on exercise endurance, intramuscular ROS/H2O2 production, and several mitochondrial function-related markers (including sirtuin 1, peroxisome proliferator-activated receptor [PPAR]-δ, peroxisome proliferator-activated receptor γ coactivator 1 [PGC-1], mitochondrial transcription factor A [TFAM], and citrate synthase activity) in mice.