《生命科学》 2022, 34(1): 62-74
脂代谢紊乱是导致慢性代谢疾病发生的主要原因之一。运动作为最经济有效的物理疗法，可通过调节成纤维细胞生长因子21 (fibroblast growth factor 21, FGF21) 的表达发挥改善脂代谢紊乱的作用。现有研究表明，脂代谢紊乱会造成机体FGF21 表达异常，其血清循环水平显著增加但靶组织受体表达降低，导致FGF21 抵抗。运动调控FGF21 的表达，并通过逆转FGF21-AND 轴功能障碍，上调PI3K/Akt 信号通路表达改善胰岛素抵抗；抑制TNF-α、MCP-1、IL-1β 等炎症因子表达，下调核因子κB 蛋白信号通路表达减轻炎症反应；提高线粒体柠檬酸合成酶活性，上调AMPK 信号通路及PGC-1α 表达增加能量消耗；介导脂质重塑并调控WAT“褐变”，上调AMPK/ULK1 信号通路表达增加脂解等改善脂质代谢紊乱。运动量的累积是造成FGF21 表达发生适应性改变的关键因素，大强度(80%~85% VO2max) 的急性运动刺激或长周期( ≥ 12周) 的运动干预可有效地促进FGF21 的表达。该文以脂代谢紊乱与FGF21 的关系为切入点，对运动调控FGF21 改善脂代谢紊乱的生物学机制进行分析，并梳理不同运动调控FGF21 表达的差异，旨在为FGF21介导下改善脂代谢紊乱的运动干预方案提供指导意见。
通讯作者：郜卫峰 , Email:firstname.lastname@example.org
Disturbance of lipid metabolism is one of the main causes of chronic metabolic diseases. As the costeffective physical therapy, exercise can improve the disturbance of lipid metabolism by regulating the expression of the fibroblast growth factor 21 (FGF21). The present studies have shown that disturbance of lipid metabolism could cause abnormal expression of FGF21 in the body, and its serum circulation level increased significantly but the expression of target tissue receptor decreased, leading to FGF21 resistance. Exercise regulates the expression of FGF21and improve lipid netabolism disorders through a series of mechanisms, such as reversing the dysfunction of FGF21-AND axis, up-regulating the expression of PI3K/Akt signaling pathway to improve insulin resistance; inhibiting the expression of inflammatory factors such as TNF-α, MCP-1, IL-1β, and down-regulating the expression of nuclear factor κB protein signaling pathway to reduce inflammation; Increasing mitochondrial citrate synthase activity, up-regulating the expression of AMPK signaling pathway and PGC-1α to increase energy consumption; mediating lipid remodeling and regulating WAT "browning", up-regulating the expression of AMPK/ULK1 signaling pathway to increase lipolysis, and so on. The accumulation of exercise is the critical factor causing adaptive changes in FGF21 expression. Acute exercise stimulation with high intensity (80%~85% VO2max) or long period (≥12 weeks) exercise intervention can effectively promote the expression of FGF21. Based on the relationship between lipometabolic disturbances and FGF21, this article analyzed the biological mechanism of improving disturbance of lipid metabolism by exercise-regulated FGF21, and sorted out the differences in expression of FGF21 regulated by different exercise, in order to provide guidance for the exercise intervention program to improve disturbed lipid metabolism mediated by FGF21.
Communication Author：GAO Wei-Feng , Email:email@example.com