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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    • "Although complete separation of these components cannot be achieved, the separation conditions performed in this paper allow isolation of a fraction particularly enriched in dietary remnants, as also shown by fatty acid composition of particles, which reflects the composition of the dietary-based meal (Table 1 ). Given the difficulties involved in carrying out this kind of study with human isolated postprandial particles, a number of studies by us and others have been performed using model chylomicron remnant-like particles [26,39]. To our knowledge, this is the first study that has investigated the effects of TGRL on the secretion of chemoattractants by macrophages using human fresh ppTGRL and primary human macrophages. "
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    ABSTRACT: This study tested the hypothesis that postprandial triglyceride-rich lipoproteins (ppTGRL) have inflammatory effects in primary human monocyte-derived macrophages (HMDM). ppTGRL were isolated from normolipidemic human volunteers, and the production of chemokines and of inflammatory prostaglandins and leukotrienes via the arachidonic acid cascade in HMDM was determined, and their effect on monocyte chemotaxis were assessed. In addition, the possible role of extracellular lipases in the inflammatory effects of ppTGRL was evaluated. ppTGRL were found to increase the secretion of chemoattractants, including monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1α and -1β and IL-8, by HMDM and to have a stimulatory effect on monocyte chemotaxis. HMDM secretion of leukotrienes B4 (LTB4) and lipoxin A (LXA4), which are potent activators of monocyte migration, was also stimulated by ppTGRL. Inclusion of the lipoprotein lipase (LPL) inhibitor orlistat did not alter the effects of ppTGRL on chemokine production, and the expression of mRNA for LPL and other secreted lipases was unaffected by the lipoproteins. These findings support the hypothesis that ppTGRL induce the secretion of chemokines by macrophages which promote monocyte recruitment, and that extracellular lipolysis of the particles is not required for these effects and provide further evidence to indicate that the postprandial lipoproteins contribute to a pro-atherogenic pattern after a fat-rich meal.
    Full-text · Article · May 2013 · Cytokine
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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.
    Full-text · Article · Jan 2012 · International journal of vascular medicine
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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.
    Full-text · Article · Nov 2011 · Nutrition, metabolism, and cardiovascular diseases: NMCD
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