Fatty acid composition of chylomicron remnant-like particles influences their uptake and induction of lipid accumulation in macrophages.
ABSTRACT The influence of the fatty acid composition of chylomicron remnant-like particles (CRLPs) on their uptake and induction of lipid accumulation in macrophages was studied. CRLPs containing triacylglycerol enriched in saturated, monounsaturated, n-6 or n-3 polyunsaturated fatty acids derived from palm, olive, corn or fish oil, respectively, and macrophages derived from the human monocyte cell line THP-1 were used. Lipid accumulation (triacylglycerol and cholesterol) in the cells was measured after incubation with CRLPs for 5, 24 and 48 h, and uptake over 24 h was determined using CRLPs radiolabelled with [3H]triolein. Total lipid accumulation in the macrophages was significantly greater with palm CRLPs than with the other three types of particle. This was mainly due to increased triacylglycerol concentrations, whereas changes in cholesterol concentrations did not reach significance. There were no significant differences in lipid accumulation after incubation with olive, corn or fish CRLPs. Palm and olive CRLPs were taken up by the cells at a similar rate, which was considerably faster than that observed with corn and fish CRLPs. These findings demonstrate that CRLPs enriched in saturated or monounsaturated fatty acids are taken up more rapidly by macrophages than those enriched in n-6 or n-3 polyunsaturated fatty acids, and that the faster uptake rate results in greater lipid accumulation in the case of saturated fatty acid-rich particles, but not monounsaturated fatty acid-rich particles. Thus, dietary saturated fatty acids carried in chylomicron remnants may enhance their propensity to induce macrophage foam cell formation.
- [show abstract] [hide abstract]
ABSTRACT: The effect of the fatty acid composition of chylomicrons on the uptake and processing of the cholesterol they carry was investigated in the rat in vivo. Rats kept on a standard low fat pellet diet and tube fed a single dose of palm, olive, corn or fish oil (rich in saturated, n-9 monounsaturated, n-6 polyunsaturated and n-3 polyunsaturated fatty acids, respectively) were used to prepare [3H]cholesterol-labelled chylomicrons of different fatty acid composition. These were then injected intravenously into rats (kept on the standard diet), and the clearance of radioactivity from the blood, distribution in the plasma lipoprotein density fractions, uptake by the liver and appearance in the bile were studied. [3H]Cholesterol from fish and corn oil chylomicrons was cleared from the blood more rapidly than that from palm and olive oil chylomicrons. After 180 min the proportion of the radioactivity present in the plasma in high density lipoprotein (HDL) was less when the chylomicrons were derived from palm oil as compared to any of the other oils. Approx. 40% of the administered label was recovered in the liver after 180 min in all experiments. The percentage of the injected radioactivity secreted into bile during 180 min was significantly higher with corn and fish oil chylomicrons than with palm oil chylomicrons, with chylomicrons from olive oil in an intermediate position, and these differences were most pronounced between 60 and 120 min after administration of the label. These studies clearly demonstrate that the fatty acid composition of chylomicrons has important effects on the hepatic uptake and processing of the cholesterol they carry, with enrichment with polyunsaturated fatty acids leading to an increased rate of uptake and more rapid removal from the body via the bile as compared to enrichment with saturated or monounsaturated fatty acids.Biochimica et Biophysica Acta 11/1995; 1258(3):328-36. · 4.66 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Recent studies have demonstrated the presence of unesterified cholesterol-rich, liposome-like vesicles in the extracellular space of atherosclerotic lesions in humans and animals. Liposome-like vesicles accumulate in the subendothelial space in rabbits within 2 weeks of initiation of cholesterol feeding, well before foam cells appear. These observations suggest that extracellular liposome-like vesicles may play a pivotal role in atherogenesis. The origin of these particles is unknown. We report a combination of in vivo and in vitro experiments that suggest a novel origin for these liposome-like vesicles. We demonstrate that the liposome-like particles isolated from postmortem human atherosclerotic plaques are rich in intact apolipoprotein (apo) A-I, C apolipoproteins, and sphingomyelin. We show that the in vivo derived particles are virtually identical, structurally and compositionally, to liposome-like lipolytic surface remnants of triglyceride (TG)-rich lipoproteins produced during in vitro lipolysis of hypertriglyceridemic serum. In vitro lipolysis of isolated very-low-density lipoprotein has shown that the lipolytic surface remnants remain attached to the core remnants in the absence of high-density lipoprotein (HDL), dissociate to form liposome-like vesicles in the presence of low levels of HDL, and are assimilated into HDL to form larger HDL particles in the presence of excess HDL. Thus, the in vitro produced, liposome-like particles represent a complex of lipolytic surface remnants of TG-rich lipoproteins and apo A-I derived from HDL. Two possible origins have been suggested for the extracellular liposome-like vesicles in atherosclerotic plaques: (1) modified, aggregated, and/or degraded LDL particles entrapped in an intimal matrix and (2) intracellular lipid products of arterial wall cells. Neither possibility directly explains the presence of A-I and C apolipoproteins and excess sphingomyelin that we observe. We propose as an alternate explanation that the in vivo liposome-like particles are lipolytic surface remnants of TG-rich lipoproteins. We further suggest that these remnants are produced in the intimal space by undefined processes and/or are transcytosed into the intima from the plasma compartment as a product of normal lipolysis gone awry. We conjecture that one role of HDL may be to assimilate the highly atherogenic liposome-like particles in a (1) "mop-up" fashion to remove them from the artery wall and/or (2) preventive fashion in the plasma compartment to prevent their transcytosis into the artery wall. The suggestion that elevated concentrations of surface remnants act as a "sink" for apo A-I can also account for the well-established but poorly understood link between hypertriglyceridemia and low HDL.Arteriosclerosis and thrombosis: a journal of vascular biology / American Heart Association 05/1994; 14(4):622-35.
- [show abstract] [hide abstract]
ABSTRACT: During the postprandial state, dietary lipid is transported from the intestine to peripheral tissues by plasma lipoproteins called chylomicrons. In the capillary beds of peripheral tissues, chylomicron triglycerides are lipolyzed by the enzyme, lipoprotein lipase, allowing the delivery of free fatty acids to the cells. As a result, this produces a new particle of smaller size and enriched with cholesteryl ester referred to as chylomicron remnants. These particles are rapidly removed from the blood primarily by the liver. The liver has a complex chylomicron remnant removal system which is comprised of a combination of different mechanisms that include the low-density-lipoprotein receptor (LDLR) and the LDLR-related-protein (LRP). Furthermore, it has been suggested that there is a sequestration component whereby chylomicron remnants bind to heparan sulfate proteoglycans (HSPG) and/or hepatic lipase; this is then followed by transport to one or both of the above receptors for hepatic uptake. Over the years, a major concern has arisen about the association of chylomicron remnants and coronary heart disease (CHD) in man. Slow removal of chylomicron remnants, as reflected by a prolonged postprandial state, is now commonly observed in patients with CHD and those that have abnormal lipid disorders such as hypertriglyceridemia, familial hypercholesterolemia, familial combined hyperlipidemia and non-insulin-dependent-diabetes-mellitus. The present review will focus on (a) the details of the metabolic pathway (exogenous pathway) that describes the two-step processing of postprandial lipoproteins, (b) the role of the liver, the receptors, and the importance of efficient removal of chylomicron remnants from the blood circulation, and (c) the potential atherogenic effects of chylomicron remnants on the arterial wall.Frontiers in Bioscience 04/2001; 6:D332-54. · 3.29 Impact Factor