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.