Applications of Danio rerio as a model for studying NAFLD and NASH

The global prevalence of nonalcoholic fatty liver disease (NAFLD) has increased significantly, with a notable progression to nonalcoholic steatohepatitis (NASH), increasing risks of fibrosis and hepatocellular carcinoma. Despite numerous therapeutic interventions, efficacious treatments remain limited. Animal models, particularly rodents, are commonly used in research, but pose challenges due to various concerns. They also have many limitations regarding multi-staged systemic diseases (such as NAFLD). Therefore, it seems using a short-term in vivo model with minimal requirements would facilitate NAFLD research or drug screening projects. Zebrafish (Danio rerio) represent as a promising alternative due to their unique features, making them suitable for studying NAFLD mechanisms and drug screening. This article reviews zebrafish models for NAFLD and NASH, discussing their advantages, pathophysiological insights, and key metabolic pathways involved in disease progression. Various induction methods including dietary, genetic, and chemical approaches are explored, alongside relevant molecular biomarkers. Additionally, the translational relevance of zebrafish in drug development has been taken into account, highlighting tested pharmacological interventions. While zebrafish provide valuable insights into lipid metabolism and inflammatory pathways, some limitations, such as differences in fibrosis progression compared to mammals, must be acknowledged. Overall, zebrafish models offer a robust platform for NAFLD/NASH research, paving the way for potential therapeutic discoveries.