PUBLICATION
High-Fat Diet-Induced Diabetic Cardiomyopathy in Female Zebrafish: Cardiac Pathology and Functional Decline Mediated by Type 2 Diabetes
- Authors
- Huang, S., Chen, Z., Li, H., Zou, Y., Wang, B., Zhao, W., Zheng, L., Zhou, Z., Peng, X., Tang, C.
- ID
- ZDB-PUB-250713-8
- Date
- 2025
- Source
- Nutrients 17: (Journal)
- Registered Authors
- Zhou, Zuoqiong
- Keywords
- diabetic cardiomyopathy, high-fat diet, mitochondrial dysfunction, zebrafish model
- MeSH Terms
-
- Animals
- Diabetes Mellitus, Type 2*/complications
- Diabetes Mellitus, Type 2*/physiopathology
- Diabetic Cardiomyopathies*/etiology
- Diabetic Cardiomyopathies*/pathology
- Diabetic Cardiomyopathies*/physiopathology
- Diet, High-Fat*/adverse effects
- Disease Models, Animal
- Echocardiography
- Female
- Fibrosis
- Glucose Intolerance
- Insulin Resistance
- Myocardium/metabolism
- Myocardium/pathology
- Oxidative Stress
- Zebrafish
- PubMed
- 40647313 Full text @ Nutrients
Citation
Huang, S., Chen, Z., Li, H., Zou, Y., Wang, B., Zhao, W., Zheng, L., Zhou, Z., Peng, X., Tang, C. (2025) High-Fat Diet-Induced Diabetic Cardiomyopathy in Female Zebrafish: Cardiac Pathology and Functional Decline Mediated by Type 2 Diabetes. Nutrients. 17:.
Abstract
Background 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.
Methods 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).
Results 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.
Conclusions 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping