Fatty acid composition of chylomicron remnant-like particles influences their uptake and induction of lipid accumulation in macrophages

Department of Veterinary Basic Sciences, Royal Veterinary College, London, UK.
FEBS Journal (Impact Factor: 4). 01/2007; 273(24):5632-40. DOI: 10.1111/j.1742-4658.2006.05552.x
Source: PubMed


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.

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Available from: Javier S. Perona, Sep 16, 2014
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    • "The heparin sulphate proteoglycans that bind apo B lipoproteins may have greater affinity for TRL remnants because of cooperative apolipoprotein binding domains principally between apo B and apo E and exacerbates as a consequence of diabetes [51]. Moreover, apo E facilitates unabated uptake of remnant lipoproteins by macrophages via alternate pathways without the requisite of lipoprotein modification such as oxidation [52, 53]. "
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    ABSTRACT: Postprandial hyperlipidemia with accumulation of remnant lipoproteins is a common metabolic disturbance associated with atherosclerosis and vascular dysfunction, particularly during chronic disease states such as obesity, the metabolic syndrome and, diabetes. Remnant lipoproteins become attached to the vascular wall, where they can penetrate intact endothelium causing foam cell formation. Postprandial remnant lipoproteins can activate circulating leukocytes, upregulate the expression of endothelial adhesion molecules, facilitate adhesion and migration of inflammatory cells into the subendothelial space, and activate the complement system. Since humans are postprandial most of the day, the continuous generation of remnants after each meal may be one of the triggers for the development of atherosclerosis. Modulation of postprandial lipemia by lifestyle changes and pharmacological interventions could result in a further decrease of cardiovascular mortality and morbidity. This paper will provide an update on current concepts concerning the relationship between postprandial lipemia, inflammation, vascular function, and therapeutic options.
    International journal of vascular medicine 01/2012; 2012(9):947417. DOI:10.1155/2012/947417
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    • "Data from this laboratory and others has demonstrated that CMR are taken up by human macrophages derived from the human monocyte cell line THP-1 or from macrophages derived from freshly isolated monocytes [14,15] inducing foam cell formation [16], expression of genes involved in lipid metabolism [17] and modulation of pro-inflammatory cytokine expression [18,19]. Furthermore, CMR inhibit endothelium-dependent relaxation of isolated arteries [8,20,21], and trigger pro-inflammatory signal transduction in human endothelial cells (EC; [22]). "
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    ABSTRACT: Atherosclerosis is known to be an inflammatory disease and there is increasing evidence that chylomicron remnants (CMR), the lipoproteins which carry dietary fats in the blood, cause macrophage foam cell formation and inflammation. In early atherosclerosis the frequency of activated monocytes in the peripheral circulation is increased, and clearance of CMR from blood may be delayed, however, whether CMR contribute directly to monocyte activation and subsequent egress into the arterial wall has not been established. Here, the contribution of CMR to activation of monocyte pro-inflammatory pathways was assessed using an in vitro model. Primary human monocytes and CMR-like particles (CRLP) were used to measure several endpoints of monocyte activation. Treatment with CRLP caused rapid and prolonged generation of reactive oxygen species by monocytes. The pro-inflammatory chemokines MCP-1 and IL-8 were secreted in nanogram quantities by the cells in the absence of CRLP. IL-8 secretion was transiently increased after CRLP treatment, and CRLP maintained secretion in the presence of pharmacological inhibitors of IL-8 production. In contrast, exposure to CRLP significantly reduced MCP-1 secretion. Chemotaxis towards MCP-1 was increased in monocytes pre-exposed to CRLP and was reversed by addition of exogenous MCP-1. Our findings indicate that CRLP activate human monocytes and augment their migration in vitro by reducing cellular MCP-1 expression. Our data support the current hypothesis that CMR contribute to the inflammatory milieu of the arterial wall in early atherosclerosis, and suggest that this may reflect direct interaction with circulating blood monocytes.
    Nutrition, metabolism, and cardiovascular diseases: NMCD 11/2011; 21(11):871-8. DOI:10.1016/j.numecd.2010.02.019 · 3.32 Impact Factor
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    • "To mimic the physiologic situation as closely as possible, in this study, we used CRLPs containing TG derived from palm, olive, or corn oils so that the particles were enriched in the fatty acids predominating in the oils but, as in vivo, also contained a complex mixture of other fatty acids. In earlier work in our laboratory [39], we have shown that the fatty acid composition of CRLPs containing TG from palm, olive, and corn oil is similar to that of the parent oils and also that of rat physiologic CMR derived from them [38]; thus, the palm, olive, or corn CRLPs were enriched in SFA (mainly palmitic acid, 16:0), MUFA (mainly oleic acid, 18:1n-9), and n-6 PUFA (mainly linoleic acid, 18:2n-6), respectively. There were no significant differences, however, in the TG or TC content, the TG/TC ratio, or the apo E content (Table 2, Fig. 1) of the 3 types of particles. "
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    ABSTRACT: The influence of dietary fats carried in chylomicron remnants on the hepatic secretion of very low-density lipoprotein (VLDL) was investigated using chylomicron remnant-like particles (CRLPs) and cultured rat hepatocytes as the experimental model. Chylomicron remnant-like particles containing triacylglycerol (TG) from palm, olive, or corn (enriched in saturated, monounsaturated, or n-6 polyunsaturated fatty acids) oil, respectively, were incubated with cultured hepatocytes for 5 hours. The medium was then removed and replaced with medium without CRLPs; and the secretion of TG, cholesterol, and apolipoprotein B48 during the following 16 hours was determined. Secretion of TG into the d less than 1.050-g/mL fraction containing VLDL was unaffected by olive CRLPs, but was significantly increased in cells exposed to palm or corn CRLPs in comparison with both olive CRLPs and control incubations without CRLPs. Secretion of apolipoprotein B48, however, was not changed by any of the CRLP types. Apolipoprotein B messenger RNA levels were decreased by olive and corn CRLPs, and 3-hydroxy-3-methylglutaryl coenzyme A reductase messenger RNA abundance was increased by palm CRLPs; but expression of other genes involved in the regulation of VLDL secretion was unaffected. These findings demonstrate that CRLPs enriched in saturated fatty acids or n-6 polyunsaturated fatty acids increase the secretion of TG in VLDL, possibly because of the secretion of larger particles, whereas those enriched in monounsaturated fatty acids have no effect. Thus, different dietary fats have differential effects on VLDL secretion directly when delivered to the liver in chylomicron remnants.
    Metabolism: clinical and experimental 03/2009; 58(2):186-95. DOI:10.1016/j.metabol.2008.09.012 · 3.89 Impact Factor
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