Flaxseed oil containing flaxseed oil ester of plant sterol attenuates high-fat diet-induced hepatic steatosis in apolipoprotein-E knockout mice

• Flaxseed oil ester of plant sterol (FO-PS) improved hepatic steatosis in apoE−/− mice.
• Lipid metabolism regulation may be one of mechanisms by which FO-PS prevented hepatic steatosis.
• Alleviated effect of FO-PS on hepatic steatosis was associated with oxidative stress reduction.
• FO-PS protected against hepatic steatosis by inhibiting system inflammation response.

The prevalence of non-alcoholic fatty liver disease (NAFLD) has dramatically increased globally during recent decades. Dietary flaxseed oil and plant sterol exert potential benefit to NAFLD. Present study was designed to evaluate the effects of flaxseed oil containing flaxseed oil ester of plant sterols (FO-PS) on hepatic steatosis induced by high fat diet (HFD) and investigate the underlying molecular mechanisms. C57BL/6 mice were administered a regular diet (RG) and apoE−/− mice were given HFD alone or plus 5% flaxseed oil with or without 3.3% FO-PS for 18 weeks. Our data showed that HFD induced NAFLD while dietary flaxseed oil fortified with FO-PS offered a synergistically effective strategy for improving hepatic steatosis as well as optimizing overall lipid levels, reducing oxidative stress and inhibiting system inflammation. The expression levels of hepatic genes involved in cholesterol efflux (ABCA1, LXR, SR-BI) and triacylglycerol catabolism (PPARα) were also increased significantly by intervention of flaxseed oil plus FO-PS. In addition, combination treatment reduced ROS production and down-regulated inflammatory markers (IL-6, TNF, MCP-1 and ICAM-1) in liver. Thus, dietary supplementation of flaxseed oil containing FO-PS altered the expressions of genes related to lipid metabolism and inflammation, and thus ameliorated hepatic steatosis.