Evaluating the effect of γ-oryzanol on MASLD pathology using a medaka fish model

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses liver conditions not caused by alcohol, including metabolic dysfunction-associated steatohepatitis (MASH), which involves inflammation and fibrosis, with rising global prevalence. While research to explore MASLD/MASH prevention or cure has largely relied on rodent models, ethical concerns regarding animal welfare have prompted the exploration of alternatives. This study examines the application of a recently developed medaka fish MASH/MASLD model to assess the impact of food components on liver pathology. Medaka were divided into groups and fed for 12 weeks with either a normal diet (ND), a high-fat diet (HFD), or HFD supplemented with γ-oryzanol (Ory). Liver samples were analyzed morphologically, histologically, and biochemically using GC/MS and real-time PCR, with gut microbiota composition also assessed. We show that γ-oryzanol supplementation resulted in smaller, fewer lipid droplets in the liver compared with the HFD group, while GC/MS analysis showed a decreasing trend in total and individual fatty acid content. Additionally, gut microbiota diversity improved in the Ory group. These findings align with previous rodent studies, suggesting that γ-oryzanol may suppress hepatic fat accumulation and inflammation. The study demonstrates the potential of γ-oryzanol as a functional food ingredient for preventing MASLD. Furthermore, this study supports the use of medaka as a cost-effective and ethical alternative to rodent models in food science research.