Huang Shuaiwang, Chen Zhanglin, Li Haoming, Zou Yunyi, Wang Bihan, Zhao Wenjun, Zheng Lan, Zhou Zuoqiong, Peng Xiyang, Tang Changfa
College of Physical Education, Hunan Normal University, Changsha 410012, China.
Key Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, Hunan Normal University, Changsha 410012, China.
Nutrients. 2025 Jul 2;17(13):2209. doi: 10.3390/nu17132209.
Diabetic cardiomyopathy (DCM) is characterized by progressive cardiac dysfunction, metabolic dysregulation, myocardial fibrosis, and mitochondrial impairment. Existing animal models, such as streptozotocin (STZ)-induced models, suffer from high mortality and fail to replicate chronic metabolic dysregulation induced by high-fat diets (HFD), whereas HFD or HFD/STZ-combined rodent models require high maintenance costs. This study aimed to establish a zebrafish HFD-DCM model to facilitate mechanistic exploration and drug discovery.
Eighty wild-type female zebrafish were divided into normal diet (N, 6% fat) and HFD (H, 24% fat) groups and fed the diet for 8 weeks. Metabolic phenotypes were evaluated using intraperitoneal glucose tolerance tests and insulin level analysis. Cardiac function was assessed by using echocardiography (ejection fraction, E peak). Structural, metabolic, and oxidative stress alterations were analyzed by histopathology (H&E, Masson, and Oil Red O staining), molecular assays (RT-qPCR, Western blotting), and mitochondrial structure/function evaluations (respiratory chain activity, transmission electron microscopy, and DHE staining).
HFD-fed zebrafish developed obesity, insulin resistance, and impaired glucose tolerance. Echocardiography revealed cardiac hypertrophy, reduced ejection fraction, and diastolic dysfunction. Excessive lipid accumulation, upregulated fibrosis/inflammatory markers, impaired mitochondrial respiration, elevated reactive oxygen species levels, and a disrupted redox balance were observed.
We established a female zebrafish HFD model that recapitulates human DCM features, including hypertrophy, metabolic dysregulation, fibrosis, inflammation, and mitochondrial dysfunction. This model offers novel insights into DCM pathogenesis and serves as a valuable platform for mechanistic studies and targeted drug screening.
糖尿病性心肌病（DCM）的特征是进行性心脏功能障碍、代谢失调、心肌纤维化和线粒体损伤。现有的动物模型，如链脲佐菌素（STZ）诱导的模型，死亡率高，且无法复制高脂饮食（HFD）诱导的慢性代谢失调，而HFD或HFD/STZ联合啮齿动物模型的维护成本很高。本研究旨在建立一种斑马鱼HFD-DCM模型，以促进机制探索和药物发现。
将80条野生型雌性斑马鱼分为正常饮食（N，6%脂肪）组和HFD（H，24%脂肪）组，并喂食8周。使用腹腔葡萄糖耐量试验和胰岛素水平分析评估代谢表型。通过超声心动图（射血分数、E峰）评估心脏功能。通过组织病理学（苏木精和伊红染色、Masson染色和油红O染色）、分子分析（RT-qPCR、蛋白质免疫印迹法）和线粒体结构/功能评估（呼吸链活性、透射电子显微镜和二氢乙锭染色）分析结构、代谢和氧化应激改变。
喂食HFD的斑马鱼出现肥胖、胰岛素抵抗和葡萄糖耐量受损。超声心动图显示心脏肥大、射血分数降低和舒张功能障碍。观察到脂质过度积累、纤维化/炎症标志物上调、线粒体呼吸受损、活性氧水平升高和氧化还原平衡破坏。
我们建立了一种雌性斑马鱼HFD模型，该模型概括了人类DCM的特征，包括肥大、代谢失调、纤维化、炎症和线粒体功能障碍。该模型为DCM发病机制提供了新的见解，并作为机制研究和靶向药物筛选的宝贵平台。
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