Effects of various dietary factors on the activity and gene expression of hepatic enzymes in fatty acid synthesis and oxidation were examined in the rat. Dietary soybean phospholipid profoundly decreased hepatic triacylglycerol synthesis accompanying by a marked reduction in the activity and mRNA levels of enzymes involved in fatty acid synthesis. Phospholipids from egg yolk and safflower seed origin showed similar physiological activity in reducing hepatic lipogenesis. Dietary fats rich in α-linolenic acid compared to saturated fats and a fat rich in linoleic acid increased the activity and gene expression of hepatic enzymes in fatty acid oxidation. The β-oxidation rate of α-linolenic acid, relative to palmitic and linoleic acids, was higher in both the mitochondrial and peroxisomal pathways. It was suggested that both substrate specificity and alterations in the activities of the enzymes in the β-oxidation pathway play a significant role in regulating serum lipid concentrations in rats fed α-linolenic acid. Sesamin, a sesame lignan, was found to be a potent inducer of hepatic fatty acid oxidation. Sesamin dose-dependently and profoundly increased the activity and gene expression of hepatic fatty acid oxidation enzymes. Sesamin also showed the physiological activity in reducing gene expression of hepatic lipogenic enzymes through the down-regulation of sterol element binding protein-1. Therefore, it is apparent that dietary sesamin reduces serum lipid levels through alterations in both hepatic fatty acid oxidation and synthesis.