BACKGROUND The putative role of resveratrol, a polyphenol present in grapes and other plants, in modulating dislypidemia, thus preventing cardiovascular diseases, is generally based on proliferating cell lines and in vivo studies in different pathological conditions. The aim of the present study was to investigate whether resveratrol plays a role on lipid biosynthesis in rat hepatocytes. METHODS The effect of resveratrol on total rate of fatty acid, cholesterol and complex lipid synthesis, assayed by the incorporation of [1-(14)C]acetate into these lipid fractions, was investigated in rat hepatocyte suspensions. Enzyme activities of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) as well as 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA-R), pace-setting steps of de novo fatty acid and cholesterol synthesis, respectively, were in situ measured in digitonin-permeabilized hepatocytes. RESULTS Resveratrol-treated hepatocytes exhibited a short-term (30 min) inhibition (IC(50) approximately 25 microm) of total fatty acid synthesis from [1-(14)C]acetate. Among neosynthesized fatty acids, palmitic acid formation was mainly reduced, thus suggesting that enzymatic step(s) of de novo fatty acid synthesis was affected by resveratrol. In digitonin-permeabilized hepatocytes, only ACC activity was noticeably reduced, while no change in FAS activity was observed. A noticeable resveratrol-induced reduction of label incorporation into triacylglycerols was also detected. Conversely, cholesterol synthesis and HMG-CoA-R activity were unaffected by resveratrol. CONCLUSIONS Results here reported show that in isolated hepatocytes from normal rats a resveratrol-induced short-term inhibition of fatty acid and triacylglycerol synthesis occurs. This finding may represent a potential mechanism contributing to the reported hypolipidemic effect of resveratrol.