Article

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: 3.99). 01/2007; 273(24):5632-40.
Source: PubMed

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.

0 Bookmarks
 · 
125 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Lipoprotein-apheresis (apheresis) removes LDL-cholesterol in patients with severe dyslipidemia. However, reduction is transient indicating the long-term cardiovascular benefits of apheresis may not solely be due to LDL removal. Microparticles (MPs) are submicron vesicles released from the plasma membrane of cells. MPs, particularly platelet-derived MPs, are increasingly being linked to the pathogenesis of many diseases. We aimed to characterize the effect of apheresis on MP size, concentration, cellular origin and fatty acid concentration in individuals with familial hypercholesterolemia (FH). Plasma and MP samples were collected from twelve individuals with FH undergoing routine apheresis. Tunable resistive pulse sensing (TRPS - np200) and nanoparticle tracking analysis (NTA) measured a fall in MP concentration (33% and 15% respectively, p<0.05) pre to post-apheresis. Flow cytometry showed MPs were predominantly Annexin V positive and of platelet (CD41) origin both pre- (88.9%) and post- (88.4%) apheresis. Fatty acid composition of MPs differed to that of plasma, though apheresis affected a similar profile of fatty acids in both compartments as measured by gas chromatography-flame ionization detection (GC-FID). MP concentration was also shown to positively correlate with thrombin generation potential. In conclusion, we show apheresis non-selectively removes Annexin V positive platelet-derived MPs in individuals with FH. These MPs are potent inducers of coagulation and are elevated in cardiovascular disease; this reduction in pathological MPs could relate to the long-term benefits of apheresis.
    The Journal of Lipid Research 08/2014; · 4.73 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Las grasas constituyen uno de los principios in-mediatos más importantes de nuestra alimenta-ción, con varias funciones vitales que las convier-ten en nutrientes fundamentales para el buen funcionamiento del organismo. Los ácidos grasos pueden ser almacenados en el organismo como tri-glicéridos (TG) o grasas, o formar parte de las membranas como fosfolípidos u otros lípidos de naturaleza compleja (Fig. 1). Los ácidos grasos forman parte de los TG, de los lípidos complejos y pueden esterificar el colesterol. Existen dos clases básicas de ácidos grasos, los satu-rados y los insaturados, aunque estos últimos se cla-sifican a su vez dependiendo del número de insatura- Los ácidos grasos esenciales, así como sus derivados de cadena larga n-6 y n-3 son fundamentales durante la gestación, lactancia e infancia; son necesarios para el cre-cimiento y desarrollo de todos los tejidos, y especialmente del sistema nervioso, donde su presencia en órganos espe-cializados como el cerebro y la retina es relativamente ele-vada. Por otro lado, existen distintas situaciones patológicas que también pueden modularse mediante el consumo de determinados ácidos grasos. Los procesos inflamatorios y de reparación pueden ser perjudiciales cuando se cronifi-can. Patologías como la aterosclerosis, hepatitis, enferme-dades inflamatorias del intestino, cirrosis hepática, fibrosis pulmonar, psoriasis, artritis reumatoide y otras muchas enfermedades de naturaleza autoinmune, representan al-teraciones inflamatorias crónicas, donde se producen me-diadores químicos de inflamación, llamados genéricamen-te eicosanoides, a partir de algunos ácidos grasos poliinsaturados de las membranas celulares. La mayor ac-tividad proinflamatoria de los eicosanoides derivados del ácido araquidónico (20:4 n-6) frente a los derivados del ei-cosapentaenoico (20:5 n-3) explica la acción antinflama-toria de estos últimos. Asimismo, se ha demostrado que la alimentación rica en ácido oleico disminuye la intensidad de los procesos inflamatorios en varias patologías. Palabras clave: Lípidos. Salud. Ácidos grasos. Dieta. Docosahexaenoico. Araquidónico. Oleico. Gestación. Lactancia. Procesos inflamatorios. Essenti al fatty acids and their n-6 and n-3 long chain derivatives are vital during gestation, lactation and infancy. They are indispensable for tissue growth and develop-ment, specifically in the nervous system, since high con-centration of these long-chain fatty acids have been found in specialized tissues such as brain and retina. On the other side, there are different pathologies that may be influenced by dietary fatty acid profile. Persisting inflammatory and breath processes can be harmful. A number of pathologies such as atherosclerosis, hepatitis, inflammatory bowel diseases, hepatic cirrhosis, lung fibro-sis, psoriasis, rheumatoid arthritis, and other autoimmune diseases, represent chronic inflammatory processes in which cell membrane polyunsaturated fatty acid-derived mediators, so called eicosanoids, are released. N-6 arachi-donic (20:4 n-3) derived eicosanoids are more active than n-3 eicosapentaenoic (20:5 n-3) derived molecules. Like-wise, it has been demonstrated that oleic acid rich diets may decrease inflammatory intensity of different patholo-gies.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Postprandial TAG-rich lipoproteins (TRL) can be taken up by macrophages, leading to the formation of foam cells, probably via receptor-mediated pathways. The present study was conducted to investigate whether the postprandial time point at which TRL are collected modulates this process. A meal containing refined olive oil was given to nine healthy young men and TRL were isolated from their serum at 2, 4 and 6 h postprandially. The lipid class and apoB compositions of TRL were determined by HPLC and SDS-PAGE, respectively. The accumulation of lipids in macrophages was determined after the incubation of THP-1 macrophages with TRL. The gene expression of candidate receptors was measured by real-time PCR. The highest concentrations of TAG, apoB48 and apoB100 in TRL were observed at 2 h after the consumption of the test meal. However, excessive intracellular TAG accumulation in THP-1 macrophages was observed in response to incubation with TRL isolated at 4 h, when their particle size (estimated as the TAG:apoB ratio) was intermediate. The abundance of mRNA transcripts in macrophages in response to incubation with TRL was down-regulated for LDL receptor (LDLR), slightly up-regulated for VLDL receptor and remained unaltered for LDLR-related protein, but no effect of the postprandial time point was observed. In contrast, the mRNA expression of scavenger receptors SRB1, SRA2 and CD36 was higher when cells were incubated with TRL isolated at 4 h after the consumption of the test meal. In conclusion, TRL led to excessive intracellular TAG accumulation in THP-1 macrophages, which was greater when cells were incubated with intermediate-sized postprandial TRL isolated at 4 h and was associated with a significant increase in the mRNA expression of scavenger receptors.
    British Journal Of Nutrition 09/2014; · 3.34 Impact Factor

Full-text (2 Sources)

Download
8 Downloads
Available from
Sep 16, 2014