Macrophage cholesterol efflux elicited by human total plasma and by HDL subfractions is not affected by different types of dietary fatty acids (original) (raw)
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The impact of dietary fatty acids on macrophage cholesterol homeostasis
The Journal of Nutritional Biochemistry, 2014
The impact of dietary fatty acids in atherosclerosis development may be partially attributed to their effect on macrophage cholesterol homeostasis. This process is the result of interplay between cholesterol uptake and efflux, which are permeated by inflammation and oxidative stress. Although saturated fatty acids (SAFAs) do not influence cholesterol efflux, they trigger endoplasmic reticulum stress, which culminates in increased lectin-like oxidized LDL (oxLDL) receptor (LOX1) expression and, consequently, oxLDL uptake, leading to apoptosis. Unsaturated fatty acids prevent most SAFAs-mediated deleterious effects and are generally associated with reduced cholesterol efflux, although α-linolenic acid increases cholesterol export. Trans fatty acids increase macrophage cholesterol content by reducing ABCA-1 expression, leading to strong atherosclerotic plaque formation. As isomers of conjugated linoleic acid (CLAs) are strong PPAR gamma ligands, they induce cluster of differentiation (CD36) expression, increasing intracellular cholesterol content. Considering the multiple effects of fatty acids on intracellular signaling pathways, the purpose of this review is to address the role of dietary fat in several mechanisms that control macrophage lipid content, which can determine the fate of atherosclerotic lesions.
Arteriosclerosis, Thrombosis, and Vascular Biology, 1993
This study was designed to determine whether modifications induced by dietary fats on the high-density lipoprotein3 (HDL3) physicochemical characteristics could affect cholesterol efflux and intracellular cholesterol content, leading to upregulation of low-density lipoprotein (LDL) receptor activity from cultured fibroblasts. Serum HDL3S were obtained from 12 healthy women aged 26 to 49 years who adhered to four 7-week isocaloric diets containing 30% of the caloric intake as fat. Of the total calories, 15.6% of each diet was provided by (1) milk fats, rich in saturated fatty acids; (2) sunflower oil, rich in n-6 polyunsaturated fatty acids; (3) olive oil, rich in monounsaturated fatty acids; and (4) rapeseed oil, rich in n-3 polyunsaturated fatty acids. HDL3 isolated after the monounsaturated fatty acid diet induced the greatest cellular [3H]free cholesterol efflux, reduced the content of intracellular cholesterol, and enhanced 125I-LDL degradation. Univariate regression analyses su...
British Journal of Nutrition, 2009
Dietary long-chain PUFA, both n-3 and n-6, have unique benefits with respect to CVD risk. The aim of the present study was to determine the mechanisms by which n-3 PUFA (EPA, DHA) and n-6 PUFA (linoleic acid (LA), arachidonic acid (AA)) relative to SFA (myristic acid (MA), palmitic acid (PA)) alter markers of inflammation and cholesterol accumulation in macrophages (MΦ). Cells treated with AA and EPA elicited significantly less inflammatory response than control cells or those treated with MA, PA and LA, with intermediate effects for DHA, as indicated by lower levels of mRNA and secretion of TNFα, IL-6 and monocyte chemoattractant protein-1. Differences in cholesterol accumulation after exposure to minimally modified LDL were modest. AA and EPA resulted in significantly lower MΦ scavenger receptor 1 mRNA levels relative to control or MA-, PA-, LA-and DHA-treated cells, and ATP-binding cassette A1 mRNA levels relative to control or MA-, PA-and LA-treated cells. These data suggest changes in the rate of bidirectional cellular cholesterol flux. In summary, individual long-chain PUFA have differential effects on inflammatory response and markers of cholesterol flux in MΦ which are not related to the n position of the first double bond, chain length or degree of saturation.
British Journal of Nutrition, 2008
During atherogenesis, a pathological accumulation of lipids occurs within aortic intimal macrophages through uptake of plasma oxidised LDL (oxLDL). The aim of the present study was to determine whether macrophage uptake of plasma oxLDL and LDL susceptibility to oxidation may be determined by quantity and quality of dietary fat. Twenty healthy young men were subjected to three dietary periods, each lasting 4 weeks. The first was an SFA-enriched diet (38 % fat, 20 % SFA), which was followed by a carbohydrate (CHO)-rich diet (30 % fat, , 10 % SFA, 55 % CHO) or a MUFA olive oil-rich diet (38 % fat, 22 % MUFA) following a randomised cross-over design. After each diet period, LDL particles were oxidised with Cu ions to determine LDL susceptibility to oxidation and subsequently incubated with the U937-macrophage cell line to determine the percentage of uptake of plasma oxLDL. The shift from the MUFA diet to the SFA-or CHO-rich diets reduced the resistance of LDL particles to oxidation, decreasing lag time (P¼ 0•038) and increasing the propagation rate (P¼ 0•001). Furthermore, the MUFA-rich diet demonstrated reduced macrophage uptake of plasma oxLDL (P¼ 0•031) as compared with the SFA-rich diet. Finally, macrophage uptake of plasma oxLDL was correlated (r 0•45; P¼ 0•040) with total amount of conjugated dienes after LDL oxidation. Our data suggest that a MUFA-rich diet may have favourable effects on cardiovascular risk since it prevents the oxidative modifications of LDL and reduces macrophage uptake of plasma oxLDL.
Omega 3 Fatty Acids Promote Macrophage Reverse Cholesterol Transport in Hamster Fed High Fat Diet
PLoS ONE, 2013
The aim of this study was to investigate macrophage reverse cholesterol transport (RCT) in hamster, a CETP-expressing species, fed omega 3 fatty acids (v3PUFA) supplemented high fat diet (HFD). Three groups of hamsters (n = 6/group) were studied for 20 weeks: 1) control diet: Control, 2) HFD group: HF and 3) HFD group supplemented with v3PUFA (EPA and DHA): HFv3. In vivo macrophage-to-feces RCT was assessed after an intraperitoneal injection of 3 H-cholesterol-labelled hamster primary macrophages. Compared to Control, HF presented significant (p,0.05) increase in body weight, plasma TG (p,0.01) and cholesterol (p,0.001) with an increase in VLDL TG and in VLDL and LDL cholesterol (p,0.001). Compared to HF, HFv3 presented significant decrease in body weight. HFv3 showed less plasma TG (p,0.001) and cholesterol (p,0.001) related to a decrease in VLDL TG and HDL cholesterol respectively and higher LCAT activity (p,0.05) compared to HF. HFv3 showed a higher fecal bile acid excretion (p,0.05) compared to Control and HF groups and higher fecal cholesterol excretion (p,0.05) compared to HF. This increase was related to higher gene expression of ABCG5, ABCA1 and SR-B1 in HFv3 compared to Control and HF groups (,0.05) and in ABCG1 and CYP7A1 compared to HF group (p,0.05). A higher plasma efflux capacity was also measured in HFv3 using 3 H-cholesterol labeled Fu5AH cells. In conclusion, EPA and DHA supplementation improved macrophage to feces reverse cholesterol transport in hamster fed HFD. This change was related to the higher cholesterol and fecal bile acids excretion and to the activation of major genes involved in RCT.
The Journal of Nutritional Biochemistry, 1995
At low levels of dietary cholesterol intake (<200 mglday human equivalent), the plasma cholesterol response in diSferent species (man and animals) is governed by two key dietary fatty acids: myristic acid (14:0) and linoleic acid (l&2). Thus, in human subjects and animals with presumably normal lipoprotein metabolism, 14:0-ri~hfats routinely raise the plasma cholesterol in a linear relationship, whereas l&2-rich fats lower it in a curvilinear fashion, i.e., there is a "threshold" intake of 18:2 above which a further decline in plasma cholesterol is less pronounced. Palmitic (l&O) and oleic (l&l) acids appear to be neutral under these circumstances. In situations involving impaired lipoprotein metabolism (e.g., diminished low density lipoprotein [LDL] receptor activity), or in the presence of high levels of dietary cholesterol (probably >500 mgl~y), the plasma cholesterol response is no longer described accurately by dietary 14:O and l&2 alone. in such situations 16:0 appears to contribute to plasma cholesterol elevation. The hypercholesterolemic potential of 16.0, possibly reflecting a synergism between dietary cholesterol and 1&O, is thought to reside, in part, in the ability of 16:O to increase the transport of very low density lipoprotein (VLDL) apoB. Increased production of VLDL, coupled with impaired LDL receptor activity, results in an expansion of the LDL pool when the ability to clear VLDL remnants is impaired. Evidence is also available to suggest that the position of saturated fatty acids on the TG molecule affects its hypercholesterolemic ability. An argument is made for selecting animal models for investigation of the fat saturation effect based initially on the total plasma &holesterol (TC) response, with subsequent emphasis being placed on lipoproteins and the actual control mechanism(s) once the generic similarity in the TC response with that in humans has been established. (J. Nutr. Biochem. 6:188-194, 1995.) Historical perspective Studies on diet-related cholesterolemia over the past 40 years have clearly established that saturated fats raise plasma cholesterol whereas polyunsaturated fats lower it. 'A These findings led to mass introduction of polyenes in the marketplace (since the 1950s) which doubled the typical polyene consumption between 1940 and 1985 in the United States from 2.5 to 5.5% energy.5 The rise in polyunsaturated fat intake was followed by a peak and decline in serum cholesterol and coronary heart disease.' However, despite the vast body of data, much controversy persists concerning the impact of specific dietary fatty acids on plasma choles-
The Journal of Lipid Research, 2008
The main antiatherogenic function of HDL is to promote the efflux of cholesterol from peripheral cells and transport it to the liver for excretion in a process termed reverse cholesterol transport. The aim of this study was to evaluate the cholesterol efflux capacity in low-and high-HDL subjects by utilizing monocytes and serum from 18 low-HDL and 15 high-HDL subjects. Low and high HDL levels were defined, respectively, as HDL #10 th and HDL $90 th Finnish age/sex-specific percentile. Cholesterol efflux from [ 3 H]cholesterol-oleate-acetyl-LDL-loaded monocyte-derived macrophages to standard apolipoprotein A-I (apoA-I), HDL 2 , and serum was measured. In addition, cholesterol efflux from acetyl-LDL-loaded human THP-1 macrophages to individual sera (0.5%) derived from the study subjects was evaluated. Cholesterol efflux to apoA-I, HDL 2 , and serum from macrophage foam cells derived from low-and high-HDL subjects was similar. The relative ABCA1 and ABCG1 mRNA expression levels in unloaded macrophages, as well as their protein levels in loaded macrophage foam cells, were similar in the two study groups. Cholesterol efflux from THP-1 foam cells to serum recovered from high-HDL subjects was slightly higher than that to serum from low-HDL subjects (P 5 0.046). Cholesterol efflux from THP-1 macrophages to serum from study subjects correlated with serum apoB (P 5 0.033), apoA-I (P 5 0.004), apoA-II (P , 0.0001), and the percentage of apoA-I present in the form of preb-HDL (P 5 0.0001). Our data reveal that macrophages isolated from either low-or high-HDL subjects display similar cholesterol efflux capacity to exogenous acceptors. However, sera from low-HDL subjects have poorer cholesterol acceptor ability as compared with sera from high-HDL subjects.-Nakanishi, S., R. Vikstedt, S. Söderlund, M. Lee-Rueckert, A. Hiukka, C. Ehnholm, M. Muilu, J. Metso, J. Naukkarinen, L. Palotie, P. T. Kovanen, M. Jauhiainen, and M-R. Taskinen. Serum, but not monocyte macrophage foam cells derived from low HDL-C subjects, displays reduced cholesterol efflux capacity. J. Lipid Res. 2009. 50: 183-192. Supplementary key words atherosclerosis • reverse cholesterol transport • lipoproteins This work was supported by the Sigrid Juselius Foundation (M-R.T. and M.
Journal of Lipid Research, 1988
The livers of both baboons and rhesus monkeys fed a high fat, high cholesterol diet secreted very low density lipoproteins (VLDL) that were enriched in cholesteryl ester and apoE as compared to VLDL secreted by the livers of chow-fed animals. Stimulation of macrophage cholesterol esterification by the experimental VLDL was compared to that produced by the standard B-VLDL obtained from the plasma of a rhesus monkey fed 25% coconut oil plus 2% cholesterol. This standard 0-VLDL stimulated 7to 10-fold more esterification than did the bovine albumin control. Hepatic VLDL from fat-fed animals stimulated esterification in 5774 macrophages 50 to 150% as well as did the standard 8-VLDL, even though hepatic VLDL did not display beta electrophoretic mobility on agarose gel electrophoresis. Plasma VLDL from lard-fed baboons did not exhibit beta electrophoretic mobility but did stimulate esterification in macrophages. Baboons were divided into high and low responders based on the change in plasma cholesterol levels in response to a high fat, high cholesterol diet. Both plasma and hepatic VLDL from high responders stimulated cholesterol esterification, whereas hepatic VLDL obtained from low responders or chow-fed baboons did not stimulate cholesterol esterification in macrophages. There was a strong positive correlation (r = 0.866) between the number of apoE molecules per VLDL particle in VLDL obtained from chow-fed, lard-fed, or coconut oil-fed primates and the rate of cholesterol esterification in macrophages. m Our results show that hepatic perfusate VLDL obtained from fat-and cholesterol-fed primates have compositional and functional properties usually ascribed to circulating 0-VLDL, without displaying beta mobility, and indicate that the liver may be an important source of atherogenic lipoproteins.-Soltys, P. A