Nonalcoholic　fatty　liver　disease　(NAFLD)　is　defined　by　a　nonalcohol　relevant　pathological　accumulation　of　fat　in　the　liver.　Previous　studies　have　shown　that　sesamin　exerts　antioxidant　effects　and　improves　lipid　metabolism　of　the　fatty　liver.　In　this　study,　we　hypothesized　that　sesamin　improves　lipid　homeostasis　of　Sprague-Dawley　rats　fed　a　high-fat　diet　(HFD)　by　regulating　the　expression　of　genes　related　to　de　novo　lipogenesis　and　(beta-oxidation.　We　induced　NAFLD　in　rats　with　HFD　and　examined　the　effect　of　sesamin　in　vivo.　The　results　showed　that　HFD　rats　accumulated　total　cholesterol　and　triacylglycerols　in　the　liver　and　developed　inflammation,　as　evidenced　by　the　elevation　of　interleukin-6　and　tumor　necrosis　factor-alpha　in　the　liver　and　serum.　Sesamin　attenuated　the　disease　progression　by　improving　the　blood　lipid　profile　in　a　dose-dependent　manner.　Sesamin　reduced　the　serum　levels　of　total　cholesterol,　triacylglycerols,　low-density　lipoprotein　cholesterol,　and　free　fatty　acid,　whereas　it　increased　the　level　of　high-density　lipoprotein　cholesterol.　Meanwhile,　sesamin　increased　the　activities　of　hepatic　glutathione　peroxidase　and　superoxide　dismutase　while　reducing　the　level　of　malonaldehyde　and　cytochrome　P450　2E1.　Furthermore,　higher　doses　of　sesamin　reduced　the　expression　of　liver　X　receptor　alpha　and　its　downstream　target　genes,　whereas　it　upregulated　the　peroxisome　proliferator-activated　receptor　alpha-mediated　signaling.　These　findings　suggest　that　sesamin　attenuates　diet-induced　dyslipidemia　and　inflammation　of　NAFLD　in　rats　via　mechanisms　regulated　by　liver　X　receptor　alpha　and　peroxisome　proliferator-activated　receptor　a.　(C)　2016　Elsevier　Inc.　All　rights　reserved.