Inhibitory effect of genistein on nonalcoholic fatty liver disease development in ApoE−/− mice fed a high‐fat diet

Abstract

Non‐alcoholic fatty liver disease (NAFLD) occurs in a wide variety of clinical presentations, ranging from asymptomatic hepatic steatosis to severe non‐alcoholic steatohepatitis (NASH). Recent studies reported that ApoE−/− mice fed a high‐fat diet (HFD) can be used as a model of NASH as well as arteriosclerosis. Because genistein has been shown to alleviate hepatic steatosis, we investigated the effects of genistein on the development of NASH in ApoE−/− mice. Both wildtype and ApoE−/− mice were fed either an HFD or an HFD supplemented with genistein (0.5 g/kg diet). After 24 weeks on an HFD, serum triglyceride, total cholesterol, and oxidized lipid levels were more exacerbated in ApoE−/− mice compared to wildtype mice. In addition, ApoE−/− mice exhibited higher serum monocyte chemoattractant protein 1 (MCP‐1) and alanine aminotransferase levels. Cholesterol levels in both serum and liver were alleviated by genistein in ApoE−/− mice. Furthermore, ApoE−/− mice exhibited a reduced serum MCP‐1 levels and hepatic pro‐inflammatory gene expressions (MCP‐1 and cyclooxygenase‐2) in response to genistein. In conclusion, genistein alleviated metabolic abnormalities including hypercholesterolemia and NASH in ApoE−/− mice fed an HFD. Moreover, our findings confirmed that the ApoE−/− mice fed an HFD is a promising long term NASH model. This work was supported by National Research Foundation of Korea.