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Published on: December 11, 2020
Evaluating the effect of γ-oryzanol on MASLD pathology using a medaka fish model
Yukako Ito1, Haduki Asano1, Ayano Ueki1
1Department of Clinical Nutrition, Graduate School of Comprehensive Rehabilitation, Osaka Prefecture University, Osaka, Japan.
Abstract:
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.
Insights
γ-oryzanol supplementation in medaka fish reduced liver fat accumulation and improved gut microbiota, suggesting its potential as a functional food for metabolic dysfunction-associated steatotic liver disease (MASLD) prevention.
Area of Science:
- Nutritional science and toxicology
- Comparative pathology
- Functional foods
Background:
- Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health concern.
- Rodent models are common for MASLD research but raise ethical considerations.
- Medaka fish offer a promising alternative model for studying liver disease and dietary interventions.
Purpose of the Study:
- To evaluate the efficacy of γ-oryzanol in mitigating liver pathology associated with MASLD using a medaka fish model.
- To assess the impact of dietary γ-oryzanol on liver lipid accumulation, inflammation, and gut microbiota composition.
- To validate the medaka fish model as an ethical and cost-effective alternative for food science research.
Main Methods:
- Medaka fish were fed normal diet, high-fat diet (HFD), or HFD with γ-oryzanol for 12 weeks.
- Liver tissues were analyzed morphologically, histologically, and biochemically (GC/MS, real-time PCR).
- Gut microbiota composition was assessed.
Main Results:
- γ-oryzanol supplementation reduced lipid droplet size and number in medaka livers compared to HFD.
- A decreasing trend in total and individual fatty acid content was observed with γ-oryzanol.
- Gut microbiota diversity was enhanced in the γ-oryzanol group.
Conclusions:
- γ-oryzanol demonstrates potential in suppressing hepatic fat accumulation and inflammation, aligning with rodent study findings.
- γ-oryzanol may serve as a functional food ingredient for preventing MASLD.
- Medaka fish represent a viable, ethical, and cost-effective model for food science research on liver disease.

