The binding and internalization of 125 I-labelled chylomicron remnants derived from palm, olive, corn, or fish oil (rich in saturated, monounsaturated, n-6, or n-3 polyunsaturated fatty acids, respectively) by hepatocytes from rats fed a low-fat diet or a diet supplemented with the corresponding fat for 21 days was investigated. In hepatocytes from rats fed the low-fat diet, the association of radioactivity with the cells at 4 8C (a measure of initial binding only) was similar with all types of remnants tested, but was more rapid at 37 8C (a measure of binding plus internalization) when fish oil, as compared to olive, corn or palm oil remnants, was used, and similar differences in the internalization of the particles were observed. In contrast, when hepatocytes from rats fed the fat-supplemented diets were used, the rate of association at 37 8C of remnants with cells from rats fed palm, corn or fish oil was similar, and higher than that found with cells from animals fed olive oil, and in this case these differences were mainly due to changes in the binding of the particles to the cells at 4 8C. Both excess low-density lipoprotein (LDL), which inhibits remnant uptake by the LDL receptor, and lactoferrin, which blocks the LDL receptor-related protein (LRP), were found to decrease the association of the remnants with cells from rats fed the lowfat and high-fat diets. However, in hepatocytes from animals given the low-fat diet, most of the differences between the various types of particle were retained in the presence of lactoferrin, but abolished in the presence of LDL. In contrast, in cells from rats fed the high-fat diets, the differences were reduced by both lactoferrin and LDL. These findings demonstrate that the hepatic uptake of chylomicron remnants is influenced both by the fatty acid composition of the particles, and by longer-term adaptive changes in liver tissue, and suggest that the former effects are mediated mainly by the LDL receptor, while the latter may involve both the LDL receptor and the LRP.Keywords: chylomicron remnants; dietary fat; LDL receptor; LDL receptor-related protein; hepatocytes.Fat and cholesterol from the diet are transported in the blood in triacylglycerol-rich lipoproteins called chylomicrons and chylomicron remnants, and there is now considerable evidence to suggest that the remnant lipoproteins are strongly atherogenic [1]. Remnant particles have been shown to be taken up by the aorta in vivo as efficiently as LDL in rats and rabbits [1±3], and triacylglycerol-rich lipoproteins have been isolated from human aortic intima and atherosclerotic plaque [4,5]. In addition, delayed clearance of chylomicron remnants from the circulation has been found to be correlated with the progression of atherosclerotic lesions [6±8].Chylomicron remnants arise from the hydrolytic action of lipoprotein lipase on chylomicrons, triacylglycerol-rich lipoproteins which enter the blood from the intestine after a fat-enriched meal [9,10]. This process takes place in extrahepatic capillary beds and removes ...