Fibroblast growth factor 19 alleviates palmitic acid-induced mitochondrial dysfunction and oxidative stress via the AMPK/PGC-1α pathway in skeletal muscle
Fibroblast growth factor 19 alleviates palmitic acid-induced mitochondrial dysfunction and oxidative stress via the AMPK/PGC-1α pathway in skeletal muscle
复制标题
成纤维细胞生长因子 19 通过骨骼肌中的 AMPK/PGC-1α 途径减轻棕榈酸诱导的线粒体功能障碍和氧化应激
DOI：
10.1016/j.bbrc.2020.04.002
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发表时间：
2020-06-11
影响因子：
3.1
通讯作者：
Xiao, Qian
中科院分区：
文献类型：
--
作者：
Guo, Ai;Li, Kai;Xiao, Qian
肥胖引起的脂肪异位沉积导致骨骼肌线粒体功能障碍和氧化应激，从而影响骨骼肌的质量和功能。人成纤维细胞生长因子19(FGF19)是胆汁酸合成和代谢动态平衡的重要代谢调节因子。最近的研究表明，FGF19通过扩大肌肉纤维大小来调节骨骼肌质量，并保护肌肉免受萎缩。然而，FGF19在调节骨骼肌线粒体功能和抗氧化反应中的作用仍不清楚。因此，我们研究了FGF19在棕榈酸(PA)诱导的C2C12细胞线粒体功能障碍和氧化应激中的作用。在本研究中，我们发现FGF19可以提高线粒体生物发生调节因子(PGC-1α、NRF-1和TFAM)和抗氧化反应调节因子(NRF-2和HO-1)的mRNA和蛋白表达水平，从而减轻PA诱导的线粒体功能障碍和氧化应激。然而，AMP激活的蛋白激酶(AMPK)抑制剂化合物C和PGC-1α的siRNA敲除可阻断FGF19的调节作用。综上所述，这些发现表明，FGF19可能通过AMPK/PGC-1α途径促进线粒体的生物发生和抗氧化反应，从而减弱PA对线粒体功能障碍和氧化应激的影响；因此，FGF19可能是肥胖对骨骼肌影响的潜在治疗靶点。(C)2020 Elsevier Inc.保留所有权利。
Obesity-induced fat ectopic deposition results in mitochondrial dysfunction and oxidative stress in skeletal muscle, which could impair the quality and function of the skeletal muscle. Human fibroblast growth factor 19 (FGF19) acts as a vital metabolic regulator of bile acid synthesis and metabolic homeostasis. Recent studies have shown that FGF19 regulates skeletal muscle mass through the enlargement of muscle fiber size and protects muscles from atrophy. However, the role of FGF19 in regulating mitochondrial function and the antioxidant response in skeletal muscle remains unknown. Therefore, we investigated the effect of FGF19 on palmitic acid (PA)-induced mitochondrial dysfunction and oxidative stress in C2C12 cells. In this study, we found that FGF19 can increase the mRNA and protein expression levels of mitochondrial biogenesis regulators (PGC-1 alpha, Nrf-1, and TFAM) and antioxidant response regulators (Nrf-2 and HO-1), alleviating PA-induced mitochondrial dysfunction and oxidative stress. However, the regulatory effect of FGF19 was blocked by Compound C, an AMP-activated protein kinase (AMPK) inhibitor, and siRNA knockdown of PGC-1 alpha. Taken together, these findings indicate that FGF19 might promote mitochondrial biogenesis and antioxidant response via the AMPK/PGC-1 alpha pathway, attenuating the effect of PA on mitochondrial dysfunction and oxidative stress; therefore, FGF19 might be a potential therapeutic target for the effects of obesity on skeletal muscle. (C) 2020 Elsevier Inc. All rights reserved.