Efflux of lipid from macrophages after induction of lipid accumulation by chylomicron remnants

Moore, Elizabeth Hernández; Bejta, Fatos; Avella, Michael; Suckling, Keith E.; Botham, Kathleen M.

doi:10.1016/j.bbalip.2005.04.009

Cited by 11 publications

(14 citation statements)

References 44 publications

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“…Therefore, our work is consistent with previous studies in which CRLP enriched with saturated and monounsaturated FA are taken up more rapidly by macrophages, resulting in greater lipid accumulation of saturated FA [16]. The findings that ABCA1 as well as ABCG1 mRNA and protein levels decreased are consistent with the observation of Moore et al [17] in which lipid accumulated after exposure of macrophages to CRLP is resistant to efflux. Of note, total FA content in the various media was stable even though the TG levels varied.…”

Section: Discussionsupporting

confidence: 95%

Modulation of Macrophage Fatty Acid Content and Composition by Exposure to Dyslipidemic Serum in Vitro

Wong

Kyle

Croft

et al. 2011

Lipids

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Macrophages in arterial walls accumulate lipids leading to the development of atherosclerotic plaques. However, mechanisms underlying macrophage lipid accumulation and foam cell formation are often studied without accounting for risk factors such as dyslipidemia. We investigated the effect of varying concentrations of triglyceride (TG) within physiological range on macrophage fatty acid (FA) accumulation and expression of cholesterol efflux proteins. Human monocytes were cultured in media supplemented with 10% sera containing low (0.7 mmol/L) to high (1.4 mmol/L) TG. The resulting macrophages were harvested after 10 days for analysis of FA content and composition and expression of genes involved in lipid metabolism. Exposure to higher TG and lower HDL concentrations in media increased macrophage lipid content. Macrophages exposed to higher TG had increased total FA content compared with controls (876 μg/mg protein vs. 652 μg/mg protein) and greater proportions of C16:0, C18:1 and C18:2. Macrophage expression of both ABCA1 and ABCG1 cholesterol efflux proteins were reduced when higher TG concentrations were present in the media. Expression of scavenger receptor CD36, involved in lipoprotein uptake, was also downregulated in macrophages exposed to higher TG. Culturing macrophages in conditions of higher versus lower TG influenced macrophage FA content and composition, and levels of regulatory proteins. Replicating in vitro levels of dyslipidemia encountered in vivo may provide an informative model for investigation of atherogenesis.

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Section: Discussionsupporting

confidence: 95%

Modulation of Macrophage Fatty Acid Content and Composition by Exposure to Dyslipidemic Serum in Vitro

Wong

Kyle

Croft

et al. 2011

Lipids

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“…In order to investigate whether this is also true for CMRs, we used fluorescence labelled CRLPs to evaluate the subcellular localization of the lipid taken up by the cells. The results showed that CRLP lipid is substantially co-localized with the lysosomal marker, lysosomal associated membrane protein-1 (Figure 3) [37], and similar results were obtained with oxCRLPs and CRLPs containing probucol.…”

Section: The Efflux Of Lipid From Macrophages After Exposure To Cmrssupporting

confidence: 75%

“…After exposure of THP-1 macrophages to CRLPs (48 h) followed by incubation with or without cholesterol acceptors (24 h), we found that the mass of cholesterol was decreased only in the presence of apoA1 (apolipoprotein A1)-PC (phosphatidylcholine) vesicles, which resemble β-migrating HDL (high-density lipoprotein), a potent cholesterol acceptor, and the maximum decrease which could be achieved was 38% in 24 h. The mass of TAG was not decreased in any conditions [37]. Furthermore, investigation of the rate of efflux of lipid from THP-1 macrophages after loading the cells with CRLPs radiolabelled with [ 3 H]cholesterol or [ 3 H]triolein showed that less than 30% of the cholesterol label was removed from the cells in the presence of apoA1-PC in 24 h (Figure 2), less than 4% of the TAG label was effluxed in the same period, and there was little metabolism of the TAG taken up by the macrophages.…”

Section: The Efflux Of Lipid From Macrophages After Exposure To Cmrsmentioning

confidence: 58%

“…Furthermore, investigation of the rate of efflux of lipid from THP-1 macrophages after loading the cells with CRLPs radiolabelled with [ 3 H]cholesterol or [ 3 H]triolein showed that less than 30% of the cholesterol label was removed from the cells in the presence of apoA1-PC in 24 h (Figure 2), less than 4% of the TAG label was effluxed in the same period, and there was little metabolism of the TAG taken up by the macrophages. Oxidation of the CRLPs had no effect on the mass of cholesterol and TAG found in the cells or effluxed into the medium (Figure 2) [37]. Thus the lipid accumulated in macrophages in response to CMRs is resistant to efflux, as has been found with oxLDL [35,36].…”

Section: The Efflux Of Lipid From Macrophages After Exposure To Cmrsmentioning

confidence: 92%

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The induction of macrophage foam cell formation by chylomicron remnants

Botham

Moore

Pascale

et al. 2007

Biochemical Society Transactions

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The accumulation of foam cells in the artery wall causes fatty streaks, the first lesions in atherosclerosis. LDL (low-density lipoprotein) plays a major role in foam cell formation, although prior oxidation of the particles is required. Recent studies, however, have provided considerable evidence to indicate that CMRs (chylomicron remnants), which carry dietary lipids in the blood, induce foam cell formation without oxidation. We have shown that CMRs are taken up by macrophages and induce accumulation of both triacylglycerol and cholesterol, and that the rate of uptake and amount of lipid accumulated is influenced by the type of dietary fat in the particles. Furthermore, oxidation of CMRs, in striking contrast with LDL, inhibits, rather than enhances, their uptake and induction of lipid accumulation. In addition, the lipid accumulated after exposure of macrophages to CMRs is resistant to efflux, and this may be due to its sequestration in lysosomes. These findings demonstrate that CMRs induce pro-atherogenic changes in macrophages, and that their effects may be modulated by dietary factors including oxidized fats, lipophilic antioxidants and the type of fat present.

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“…In previous studies, CM remnants have been shown to induce extensive lipid accumulation in a variety of macrophage types, including those derived from the human monocyte cell line THP-1 (Moore et al, 2005). The exact mechanisms by which TRL are taken up by macrophages are not yet clearly defined.…”

Section: Introductionmentioning

confidence: 99%

Minor components of pomace olive oil enhance VLDL-receptor expression in macrophages when treated with postprandial triglyceride-rich lipoproteins

Cabello-Moruno

Sinausía

Montero³

et al. 2015

Grasas y Aceites

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SUMMARY:Pomace olive oil (POO) is rich in minor components, which can modulate the composition of postprandial triglyceride-rich lipoproteins (TRL) and their uptake by macrophages. The aim of the present study was to investigate the effects of postprandial TRL obtained after the ingestion of meals containing POO or refined olive oil (ROO) on foam cell formation, one of the initial steps of atherogenesis. Meals were administered to 9 healthy men and TRL were isolated from serum 4h after the intake. POO intake led to TRL with lower triglyceride/apo B48 and triglyceride/apo B100 ratios compared to ROO. Upon incubation of THP-1 macrophages with the TRL, an increase in the intracellular triglyceride content and foam cell formation was observed. Compared to ROO-TRL, the only receptor involved in lipoprotein uptake that showed changes in the mRNA expression after treatment with POO-TRL was the VLDL-receptor (VLDLr). In conclusion, the intake of POO modified the composition of human TRL, which increased the VLDLr gene expression in macrophages. However, the changes were not sufficient to enhance foam cell formation. KEYWORDS:Macrophages; Pomace olive oil; Postprandial; Triglycerides; VLDL-receptor RESUMEN: Los componentes menores del aceite de oliva de orujo aumentan la expresión del receptor VLDL en macrófagos tratados con lipoproteínas ricas en triglicéridos postprandiales. El aceite de orujo de oliva (AOO) es rico en componentes menores que pueden modular la composición de lipoproteínas ricas en triglicéridos postprandiales (TRL) y su captación por macrófagos. El objetivo del presente estudio fue investigar los efectos de TRL obtenidas después de la ingesta de comidas que contenían AOO o aceite de oliva refinado (AOR) sobre la formación de células espumosas, uno de los pasos iniciales de la aterogénesis. Las comidas fueron administradas a 9 hombres sanos y las TRL fueron aisladas del suero sanguíneo 4h después de la ingesta. La ingesta de AOO dio lugar a TRL con menor ratio triglicéridos/apo B48 y triglicéridos/apo B100 en comparación con AOR. Tras la incubación de macrófagos THP-1 con las TRL, se observó un aumento en el contenido de triglicéridos intracelular y la formación de células espumosas. En comparación con TRL-AOR, el único receptor implicado en la captación de lipoproteínas que mostró cambios en la expresión génica después del tratamiento con TRL-AOO fue el receptor VLDL (VLDLr). En conclusión, la ingesta de AOR modificó la composición de TRL humanas, lo que aumentó la expresión de VLDLr en macrófagos, aunque los cambios no fueron suficientes para mejorar la formación de células espumosas.

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Efflux of lipid from macrophages after induction of lipid accumulation by chylomicron remnants

Cited by 11 publications

References 44 publications

Modulation of Macrophage Fatty Acid Content and Composition by Exposure to Dyslipidemic Serum in Vitro

Modulation of Macrophage Fatty Acid Content and Composition by Exposure to Dyslipidemic Serum in Vitro

The induction of macrophage foam cell formation by chylomicron remnants

Minor components of pomace olive oil enhance VLDL-receptor expression in macrophages when treated with postprandial triglyceride-rich lipoproteins

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