Fibroblast growth factor 19 improves cardiac function and mitochondrial energy homoeostasis in the diabetic heart
Fibroblast growth factor 19 improves cardiac function and mitochondrial energy homoeostasis in the diabetic heart
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成纤维细胞生长因子 19 改善糖尿病心脏的心脏功能和线粒体能量稳态
DOI：
10.1016/j.bbrc.2018.09.046
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发表时间：
2018
影响因子：
3.1
通讯作者：
Zhou Yuhong
中科院分区：
文献类型：
--
作者：
Xu Wei;Wang Yongshun;Guo Yibo;Liu Jingjin;Ma Lijia;Cao Wei;Yu Bo;Zhou Yuhong
在糖尿病心肌病中，线粒体脂肪酸氧化超过线粒体葡萄糖氧化，导致代谢紊乱。成纤维细胞生长因子19（FGF 19）作为一种代谢调节因子，可能对糖尿病心肌病具有心脏保护作用。在这项研究中，我们研究了FGF 19对能量代谢的影响。糖尿病心脏的FGF 19治疗表现出较高的葡萄糖摄取和较低的脂质分布，表明能量代谢的变化。FGF 19的保护作用通过上调PGC-1α表达来防止糖尿病心脏的心室功能障碍并改善线粒体功能。另一方面，通过siRNA敲低PGC-1α减弱了FGF 19对线粒体功能和能量效率的增强作用。总之，这些结果表明FGF 19表现出改善的线粒体效率，这可能与糖尿病心脏中较高的心脏收缩力相关。还值得注意的是，调节PGC-1α（其负责FGF 19的激活）可能是糖尿病心肌病的治疗靶点。
In diabetic cardiomyopathy, mitochondrial fatty acid oxidation dominates over mitochondrial glucose oxidation, leading to metabolic disturbances. Fibroblast growth factor 19 (FGF19) acts as a metabolic regulator and may have a cardioprotective role on diabetic cardiomyopathy. In this study, we investigated the effects of FGF19 on energy metabolism. FGF19 treatment of diabetic hearts exhibited higher glucose uptake and lower lipid profiles, suggesting changes in energy metabolism. The protective effects of FGF19 prevented ventricular dysfunction in diabetic hearts and improved mitochondrial function by the upregulation of PGC-1α expression. On the other side, knockdown of PGC-1α by siRNA attenuated the effects of FGF19 on the enhancement of mitochondrial function and energy efficiency. Taken together, these results show that FGF19 exhibited improved mitochondrial efficiency, which might be associated with higher cardiac contractility in diabetic hearts. It is also of note that modulation of PGC-1α, which is responsible for the activation by FGF19, may be a therapeutic target for diabetic cardiomyopathy.