Alpha-Tocopherol Suppresses Hepatic Steatosis By Increasing Cpt-1 Expression In A Mouse Model Of Diet-Induced Nonalcoholic Fatty Liver Disease

Aim: Antioxidant therapy for with vitamin E appears to be effective for the treatment of nonalcoholic fatty liver diseas (NAFLD). However, the mechanism of action and optimal therapeutic dosage is unclear. The present study was undertaken to examine whether the effects of alpha-tocopherol (alpha-Toc) on NAFLD are dose-dependent in a diet-induced obese model.Methods: Male mice were fed standard chow, high-fat (HF) diet, HF diet with low-dose, or with high dose of alpha-Toc supplementation. Histological findings, triglyceride content, and the levels of protein expression related to fatty acid synthesis/oxidation such as carnitine palmitoyltransferase I (CPT-1) of liver were evaluated. In addition, 2-tetradecylglycidic acid (TDGA), a CPT-1 inhibitor, was administered to mice fed HF diet with low-dose of alpha-Toc. Finally, HepG2 cells in fat-loaded environment were treated with 0-50 mu M alpha-Toc.Results: Treatment of low-dose of alpha-Toc decreased HF-induced hepatic fat accumulation, but this finding was not observed in treatment of high dose of alpha-Toc. HF-induced reduction of CPT-1 was attenuated with low-dose of alpha-Toc but not with high dose of alpha-Toc. TDGA suppressed the improvement of histological findings in liver induced by low-dose of alpha-Toc treatment. CPT-1 expression in HepG2 cells increased in response to low-dose of alpha-Toc, but not in high dose.Conclusions: Dual action of alpha-Toc on CPT-1 protein levels was observed. The effect of vitamin E on NAFLD may be not be dose-dependent.