成纤维细胞生长因子 19 可改善糖尿病心脏的心功能和线粒体能量平衡。
Fibroblast growth factor 19 improves cardiac function and mitochondrial energy homoeostasis in the diabetic heart.
机构信息
Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China; The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, Heilongjiang Province, China.
Department of Pharmacology (The State-Province Key Laboratories of Biomedicine Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, China.
出版信息
Biochem Biophys Res Commun. 2018 Oct 20;505(1):242-248. doi: 10.1016/j.bbrc.2018.09.046. Epub 2018 Sep 20.
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.
在糖尿病性心肌病中，线粒体脂肪酸氧化占主导地位，超过了线粒体葡萄糖氧化，导致代谢紊乱。成纤维细胞生长因子 19（FGF19）作为一种代谢调节剂，可能对糖尿病性心肌病具有心脏保护作用。在这项研究中，我们研究了 FGF19 对能量代谢的影响。FGF19 治疗糖尿病心脏表现出更高的葡萄糖摄取和更低的脂质谱，表明能量代谢发生了变化。FGF19 的保护作用可预防糖尿病心脏的心室功能障碍，并通过上调 PGC-1α 的表达来改善线粒体功能。另一方面，通过 siRNA 敲低 PGC-1α 可减弱 FGF19 对增强线粒体功能和能量效率的作用。总之，这些结果表明，FGF19 表现出改善的线粒体效率，这可能与糖尿病心脏的更高心脏收缩力有关。值得注意的是，负责 FGF19 激活的 PGC-1α 的调节可能是糖尿病性心肌病的治疗靶点。
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