Abstract
Non-alcoholic fatty liver disease (NAFLD) involves excessive triacylglycerol (TG) accumulation in hepatocytes without alcohol use. Non-alcoholic steatohepatitis (NASH), the progressive stage of NAFLD, is characterized by inflammation and hepatocellular injury. Recently, it has been reported that Į-tocopherol (Į-Toc), a vitamin E isoform, is effective in the treatment of non-diabetic patients with NASH. However, the mechanism of the treatment effect of α-Toc on NASH is unknown. Additionally, there is no report on the treatment effects of vitamin E isoforms other than Į-Toc on NASH. Therefore, we investigated the protective effects of vitamin E isoforms other than Į-Toc, particularly Ȗ-tocopherol (Ȗ-Toc) and Ȗ-tocotrienol (Ȗ-T3), in in vivo and in vitro models of NAFLD and NASH. We first examined the effects of vitamin E isoforms on fatty liver in rats administered with a methionine- and choline-deficient diet (MCD), an animal model of NAFLD. Consequently, we found that Ȗ-Toc could suppress TG accumulation in the liver of rats administered with the MCD diet. We also found that a mixture of T3 isoforms significantly reduced the hepatic expression of interleukin (IL)-6 mRNA and IL-1ȕ mRNA in rats treated with tumor necrosis factor-Į/D-galactosamine, an animal model of NASH. Furthermore, we indicated a possibility that Ȗ-T3 restrains endoplasmic reticulum stress and subsequent inflammation in primary rat hepatocytes treated with palmitate by decreasing the expression of C/EBP homologous protein (CHOP) mRNA in the hepatocytes. Taken together, our findings suggested that among vitamin E isoforms other than Į-Toc, Ȗ-Toc and a mixture of T3 isoforms could protect against NAFLD and particularly Ȗ-T3 might protect against the shift of NASH from NAFLD.
