The fatty acid composition of chylomicron remnants influences their binding and internalization by isolated hepatocytes

Abstract

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 ...

Comparison of the effects of dietary saturated, mono-unsaturated and polyunsaturated fatty acids on very-low-density lipoprotein secretion when delivered to hepatocytes in chylomicron remnant-like particles

“…Since we have shown previously that CMRs derived from palm, olive or corn oil are taken up at similar rates by hepatocytes [10,11], it seems unlikely that this effect can be explained by a decreased rate of uptake of the particles enriched in MUFAs. However, our earlier studies have shown that a greater proportion of the TAG taken up by the tissue from CMRs derived from olive as compared with corn or palm oil is used for oxidation [10], thus it is possible that less fatty acid from the olive oil CRLPs is available for TAG production.…”

Saturated fat-induced changes in Sf 60–400 particle composition reduces uptake of LDL by HepG2 cells

“…The S f 60-400 TRLs are not a homogeneous fraction but contain a mixture of large VLDLs, small chylomicrons, and chylomicron remnants (43), and LRP1 is thought to play a significant role in the uptake of chylomicron remnants (41). A recent animal study that observed a slower uptake of chylomicron remnants enriched in SFAs by isolated rat hepatocytes compared with n-6 and n-3 PUFAs proposed that this was attributable to the influence of remnant fatty acid composition on the expression and/or activity of the LDL and LRP1 receptors (44).…”

Influencia de la composición en ácidos grasos de los remanentes de quilomicrones derivados de aceite de pescado o de maíz en el perfil lipídico de los hepatocitos de rata en cultivo

“…For the lipids in remnants to affect the fatty acids of lipids in hepatocytes, the particles must have interacted with the cells, and their components internalised, metabolised and incorporated. It was recently observed that remnants from fish oil are internalised more rapidly than corn oil remnants at low, but not at high, remnant concentrations (20). Based on the uptake rates given in (20), at the concentrations of remnants used in the present study, it is likely that after six hours both the fish and the corn oil particles were processed completely by the hepatocytes.…”

“…It was recently observed that remnants from fish oil are internalised more rapidly than corn oil remnants at low, but not at high, remnant concentrations (20). Based on the uptake rates given in (20), at the concentrations of remnants used in the present study, it is likely that after six hours both the fish and the corn oil particles were processed completely by the hepatocytes. In our treated cells, triacylglycerol and phospholipid levels increased in a dosedependent manner, but while triacylglycerols incorporated the PUFA predominating in each remnant type, the fatty acid profile of phospholipids was virtually unaffected.…”

“…Biochem., 59 (2), 2003 lomicrons and remnants has been shown to be determined by the type of fat consumed in the diet (19). Furthermore, in experiments with rats in vivo (7), with perfused rat liver (18), and with isolated rat hepatocytes (20), it has been shown that the type of fatty acid in remnants influences the removal of these particles from the plasma and their uptake and processing by the liver.…”