The effects of vanillylnonanamide-β-D-glucoside on lipid metabolism were studied in hyperlipidemic rats. Male Wistar rats weighing 280-290g were divided into three groups: a control group receiving a high-fat diet containing 1% cholesterol, and 0.003 and 0.03% glucoside groups receiving the high-fat diet supplemented with 0.003 and 0.03% vanillylnonanamide-β-D glucoside, respectively. All groups were fed ad libitum for 4 weeks. Both glucoside groups showed dose-dependent reductions in serum total cholesterol and triacylglycerol levels, and arteriosclerosis index in comparison with the control group. Their hepatic total lipid and triglyceride contents were also found to be lowered in a dose-dependent manner. Compared with the control group, hepatic cholesterol was lower and the fecal excretion rate of cholesterol was higher in the glucoside groups. In the 0.003% glucoside group, both acetyl-CoA carboxylase (ACC) [EC 6.4.1.2] and fatty acid synthase (FAS) activities were lower than in the other two groups. Hepatic triacylglycerol lipase (HTGL) [EC 3.1.1.3] activity was higher in the 0.03% glucoside group than in the other two groups. Lipoprotein lipase (LPL) [EC 3.1.1.34] activity and LPL mRNA abundance in adipose tissue were found to be higher in both the glucoside groups than in the control group. These results show that vanillylnonanamide-β-D-glucoside, with a slightly hot taste, has a lipid metabolism-improving effect comparable to that of capsaicin.