Effect of sesamin, a sesame lignan, on the hepatic fatty acid metabolism was examined in the rat. Increase of the dietary level of sesamin progressively increased the mitochondrial and peroxisomal fatty acid oxidation rate. Mitochondrial activity almost doubled in rats fed a 0.5% sesamin diet. Peroxisomal activity became more than 10 times higher in rats fed a 0.5% sesamin diet, compared to those fed a sesamin-free diet. Dietary sesamin also markedly increased the hepatic activity and mRNA levels of various fatty acid oxidation enzymes. In contrast, dietary sesamin decreased the hepatic activity and mRNA abundance of lipogenic enzymes. This was associated with the down-regulation of sterol regulatory element-binding protein-1, a transcriptional factor that regulates the lipogenic enzyme gene expression. Dietary sesamin significantly decreased the triacylglycerol secretion accompanying the increase in ketone body production by the perfused rat liver. It is apparent that sesamin affects the fatty acid metabolism and lipoprotein production in the liver, and hence lowers the serum lipid levels. We also developed several sesame lines with seeds containing sesamin and sesamolin at twice the concentration of conventional cultivars. Compared to a conventional cultivar, these lignan-rich sesame seeds increased the hepatic fatty acid oxidation rate and lowered the serum triacylglycerol level in the rat. Therefore, it is considered that enrichment of the lignans potentiates the characteristics of sesame in improving human health.