Usefulness of adult medaka fish as a model for the evaluation of alcoholic fatty liver

Abstract

Alcohol has long been acknowledged to be one of the main causes of hepatic disorders. In recent years, with the advancements in antiviral therapies, the relative proportion that alcoholic liver disease contributes among liver diseases has increased, necessitating the establishment of a useful model for the elucidation of the mechanism of its development. In this study, we developed a model of alcoholic liver disease using medaka, a small-sized fish known for its usefulness as a model organism. After rearing medaka in water containing ethanol for 2 months, fat deposition was observed in their livers. In addition, on the basis of the metabolomic analysis of the liver to evaluate metabolic changes resulting from ethanol administration, the increases in ethanol metabolites and changes in lipid metabolism were assessed. As minimally invasive evaluation methods, transparent medaka enabled the macroscopic evaluation of the progression of alcoholic fatty liver, while ultrasonography enabled the quantification of the fatty deposition of the liver. Furthermore, intestinal microbiota, the composition of which is important for the development of alcoholic liver disease, was evaluated. Microbiota changes similar to those of humans with alcoholic liver disease were observed. This study demonstrates that the development of liver disease and its amelioration through drugs can be easily evaluated using the present model or modifications thereof. Thus, this study is expected to be useful in the elucidation of liver disease development.