SRA

Background: Non-alcoholic fatty liver disease is a significant global health concern, affecting millions and characterized by its complexity as a multifaceted disease. Despite its prevalence, the underlying molecular mechanisms remain poorly understood. Methods: Here, we propose a novel diet-induced zebrafish model to investigate NAFLD. We validate this model through a series of histological examinations and molecular assessments, allowing us to explore the intricate pathways involved in the disease. We employ transcriptomic analysis to identify novel players associated with NAFLD progression. Results: Our findings demonstrate that zebrafish subjected to a high-fat diet exhibit weight gain, while Oil Red O staining confirms significant fat deposition in the liver. Quantitative PCR analysis reveals increased expression of lipogenic genes such as acc, fasn, hmgcs1, hmgcra, alongside markers of endoplasmic reticulum stress such as atf6, xbp1, gadd45a, ddit3 and mitochondrial unfolded protein response genes such as hspd1, hspa9, clpp, lonp1, indicating mitochondrial dysfunction which includes increased expression of genes encoding oxphos complexes, uqcrc2, cox4i1, atp5f1b. Transcriptomic profiling uncovers novel markers such as inha, gck, ces2a, id3 and dysregulated pathways related to metabolism, insulin signaling, and cellular stress responses. Conclusions: This study successfully establishes a zebrafish model that replicates key features of NAFLD, including histopathological changes and metabolic dysregulation. The validation of our model allows for a deeper exploration of the molecular landscape of NAFLD. By revealing novel biomarkers and pathways through transcriptomic analysis, our research opens new avenues for understanding the pathogenesis of NAFLD and potential therapeutic targets.