Beneficial Effect of Fish Oil on Liver Steatosis: Involvement of Kupffer Cell polarization and Inflammasome Inactivation

Abstract

Background Beneficial effect of marine derived fish oil on liver steatosis has been reported. Recently, a G protein-coupled receptor, FFA4 (aka GPR120) has been elucidated as an omega-3 fatty acid-sensing receptor. FFA4 expression in Kupffer cells and hepatocytes was reported. We investigated effect of polyunsaturated fatty acids on alcoholic fatty liver disease. As a mechanism study, we conducted experiments on inflammasome activation and Kupffer cell polarization. METHODS: Female C57/BL6 mouse were fed an ethanol or control-liquid diet with fish oil polyunsaturated fatty acids or saturated fatty acids for 2 weeks. Plasma transaminase, triglyceride levels, and liver histology were evaluated. Polarization of Kupffer cells and inflammasome activation were investigated by RT-PCR and Western analysis. RESULTS: First we confirmed FFA4 expression in Kupffer cells and hepatocytes. Liver steatosis induced by ethanol-liquid diet was deminished in mouse fed the ethanol plus fish oil diet but not corn oil diet. Fish oil supplementation also decreased plasma transaminase and triglyceride levels. Furthermore, ethanol drinking induced M1 polarization of Kupffer cells. However, fish oil administration polarized Kupffer cells into M2 phenotype. In addition mRNA expression of inflammasome components, such as NLRP3, ASC, and caspase-1 were decreased by fish oil supplementation, which led to reduced IL-1β production. SUMMARY: Supplementation of fish oil alleviated fat accumulation in a mouse model of alcoholic fatty liver disease. Fish oil inducing M2 polarization of Kupffer cells and inhibiting inflammasome activation were involved in anti-inflammatory and anti-steatosis effects of fish oil.