Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, China.
Department of Electrocardiographic, Shandong Provincial Hospital affiliated to Shandong University, Jinan, China.
J Cell Biochem. 2018 Nov;119(11):9602. doi: 10.1002/jcb.27068. Epub 2018 Sep 1.
A high-fat diet (HFD) has been associated with heart failure and arrhythmias; however, the molecular mechanisms underlying these associations are poorly understood. The mitochondria play an essential role in optimal heart performance, most of the energy for which is obtained from the oxidation of fatty acids. As such, chronic exposure to excess fatty acids may cause mitochondrial dysfunction and heart failure. To investigate the effects of a HFD on the mitochondrial function in the myocardium, 40 male rats were randomly divided into two groups and fed with either a normal diet or a HFD for 28 weeks. The myocardial lipid content, cardiac parameters and function, and mitochondrial morphology and function were evaluated. The expression of a number of genes involved in mitochondrial dynamics was measured using quantitative polymerase chain reaction and Western blot analyses. Proteomic analysis was also performed to identify the proteins affected by HFD treatment. Significant fat deposition in the myocardia, cardiac hypertrophy, and cardiac dysfunction were all observed in HFD-treated rats. Electron microscopy showed abnormal mitochondrial density and morphology. In addition, abnormal expression of genes involved in mitochondrial dynamics, decreased mitochondrial DNA copy numbers, reduced complex I-III and citrate synthase activities, and decreased mitochondrial respiration were observed in HFD-treated rats. High performance liquid chromatography showed downregulated adenosine triphosphate (ATP) and adenosine diphosphate levels and an increased adenosine monophosphate (AMP)/ATP ratio. Proteomic analysis confirmed the alteration of mitochondrial function and impaired expression of proteins involved in mitochondrial dynamics in HFD-treated rats. Mitochondrial dysfunction and impaired mitochondrial dynamics play an important role in heart dysfunction induced by a HFD, thus presenting a potential therapeutic target for the treatment of heart disease.
高脂肪饮食（HFD）与心力衰竭和心律失常有关；然而，这些关联的分子机制尚不清楚。线粒体在心脏的最佳功能中起着至关重要的作用，其中大部分能量来自脂肪酸的氧化。因此，慢性暴露于过量的脂肪酸可能导致线粒体功能障碍和心力衰竭。为了研究 HFD 对心肌中线粒体功能的影响，将 40 只雄性大鼠随机分为两组，分别用正常饮食或 HFD 喂养 28 周。评估心肌脂质含量、心脏参数和功能以及线粒体形态和功能。使用定量聚合酶链反应和 Western blot 分析测量涉及线粒体动力学的许多基因的表达。还进行了蛋白质组学分析以鉴定受 HFD 处理影响的蛋白质。在 HFD 处理的大鼠中观察到心肌中明显的脂肪沉积、心脏肥大和心脏功能障碍。电子显微镜显示线粒体密度和形态异常。此外，还观察到与线粒体动力学相关的基因表达异常、线粒体 DNA 拷贝数减少、复合物 I-III 和柠檬酸合酶活性降低以及线粒体呼吸减少。高效液相色谱显示三磷酸腺苷（ATP）和二磷酸腺苷水平降低，一磷酸腺苷（AMP）/ATP 比值升高。蛋白质组学分析证实了 HFD 处理的大鼠中线粒体功能的改变和参与线粒体动力学的蛋白质表达受损。线粒体功能障碍和线粒体动力学受损在 HFD 诱导的心脏功能障碍中起重要作用，因此为治疗心脏病提供了一个潜在的治疗靶点。
