Academic literature on the topic 'Chylomicron remnant'

Lymph chylomicrons radiolabelled in triacylglycerol and cholesteryl ester were injected into control and Watanabe heritable-hyperlipidaemic (WHHL) rabbits. Clearance of chylomicrons was slower in heterozygote and homozygote WHHL rabbits. Slower remnant clearance in WHHL rabbits was confirmed by monitoring the clearance from plasma of preformed chylomicron remnants. Use of chylomicron-like lipid emulsions injected into control and WHHL rabbits also confirmed the defect in remnant clearance in heterozygote WHHL and homozygote WHHL groups. Clearance from plasma of emulsion triolein was delayed in both WHHL groups compared with controls, owing to slower remnant clearance. The clearance from plasma of radioiodinated rabbit low-density lipoproteins (LDL) in heterozygote WHHL rabbits was the same as control rabbits. Defective chylomicron-remnant removal but normal LDL clearance in the heterozygote WHHL corresponded to elevated concentrations of plasma triacylglycerol and normal concentrations of plasma cholesterol. Receptor versus non-receptor clearances of chylomicron remnants were studied by comparing the clearance of emulsions with and without unesterified cholesterol respectively. Unlike control rabbits, there were no significant differences in the clearances of the two emulsion types in either the homozygote or heterozygote WHHL rabbits, indicating that the apolipoprotein-B100/E receptor is the primary route for clearance of chylomicron remnants from plasma.

When 810 mumol of [3H]glyceryl trioleate (TO) were infused intraduodenally over 6 h into rats, 29% of the triacylglycerol (TG) acyl groups in the mucosa were not from the infusate. We tested the hypothesis that chylomicron remnants contribute to the mucosal pool of nondietary TG acyl groups, since the acyl group composition of the chylomicron remnants was 58% oleate, compared with 90% in their parent chylomicrons. Purified 3H-labeled remnants were generated from chylomicrons formed in rats receiving TO intraduodenally, with 95% of the remnant disintegrations per minute (dpm) being in TG. The 3H-remnants were infused intravenously into rats receiving either saline or 135 mumol/h TO intraduodenally. In the saline-infused rats, 32% of the infused 3H dpm were in the proximal and 19% in the distal intestine and 32% were in the liver. In the fat-infused rats, 12% of the infused 3H dpm were in the proximal and 5% were in the distal gut and 29% were in the liver. When [3H]cholesterol-labeled remnants were infused intravenously and saline was infused intraduodenally, the percentage uptake into the mucosa was nearly the same as with the TG label, but comparable uptake by the liver increased. We conclude that the intestine competes with the liver for chylomicron remnant TG and cholesterol.

The effects of chylomicron remnants on cytoplasmic lipid loading and cell viability were assessed in cultures of human monocyte-derived macrophages and rabbit arterial smooth muscle cells. At a cholesterol concentration of 150 μg/ml, chylomicron remnants induced substantial cytoplasmic lipid loading of macrophages, but not of smooth muscle cells, within 6 h of exposure. Chylomicron remnants were found to be cytotoxic to macrophages and smooth muscle cells, although the latter were generally more resistant. Chylomicron remnants contained no detectable oxysterols (> 1 ng) and contained less non-esterified (‘free’) fatty acids than non-lipolysed nascent chylomicrons. Chylomicron-remnant-induced cytotoxicity appeared to be time- and dose-dependent. Macrophage and smooth muscle cell viability were inversely related to the production of superoxide free radicals and were significantly improved in the combined presence of superoxide dismutase and catalase. Collectively, our data suggest that, in macrophages, cell viability is compromised as a consequence of superoxide free radical production following uptake of chylomicron remnants. We would suggest that, in arterial smooth muscle cells, chylomicron-remnant-induced cell death also occurs as a consequence of superoxide free radical production. Our observations in the present study suggest that macrophage foam cells in atherosclerotic plaques might be derived from the cellular uptake of chylomicron remnants. Furthermore, arterial accumulation of chylomicron remnants might contribute to plaque destabilization as a consequence of cell death following superoxide free radical production by macrophages and smooth muscle cells.

During glyceryl trioleate absorption in the rat, mucosal triacylglycerol (TG) fatty acids have been shown to consist of only 71% exogenous oleate. Chylomicron remnants are enriched with endogenous TG fatty acids, compared with their parent chylomicrons, which consist primarily of exogenous TG fatty acids. Because enterocytes have the apolipoprotein B-100/E receptor, this study was directed at determining whether the cells can take up and metabolize chylomicron remnants and, if so, whether this was receptor mediated. Isolated enterocytes were incubated with purified 3H-labeled chylomicron remnants. The remnants were shown to be taken up by the basolateral membrane, not the apical membrane. Remnant uptake was proportional to time and number of enterocytes, and saturation kinetics were observed. Nonradiolabeled remnants, human low-density lipoprotein (LDL), anti-LDL receptor antibody, and receptor-associated protein, an LDL-related receptor inhibitor, were all shown to compete for or reduce 3H-remnant uptake. Remnants taken up by the enterocytes could not be removed on incubation with excess human LDL. Uptake was shown to be greatest in the villus tips of the proximal intestine. These studies suggest that enterocytes take up chylomicron remnants by a receptor-mediated process from their basolateral membranes and that the remnants could provide a source of endogenous TG fatty acids for the enterocytes.

AbstractTAG depleted remnants of postprandial chylomicrons are a risk factor for atherosclerosis. Recent studies have demonstrated that in the fasted state, the majority of chylomicrons are small enough for transcytosis to arterial subendothelial space and accelerate atherogenesis. However, the size distribution of chylomicrons in the absorptive state is unclear. This study explored in normolipidaemic subjects the postprandial distribution of the chylomicron marker, apoB-48, in a TAG-rich lipoprotein plasma fraction (Svedberg flotation rate (Sf>400), in partially hydrolysed remnants (Sf 20–400) and in a TAG-deplete fraction (Sf<20), following ingestion of isoenergetic meals with either palm oil (PO), rice bran or coconut oil. Results from this study show that the majority of fasting chylomicrons are within the potentially pro-atherogenic Sf<20 fraction (70–75 %). Following the ingestion of test meals, chylomicronaemia was also principally distributed within the Sf<20 fraction. However, approximately 40 % of subjects demonstrated exaggerated postprandial lipaemia specifically in response to the SFA-rich PO meal, with a transient shift to more buoyant chylomicron fractions. The latter demonstrates that heterogeneity in the magnitude and duration of hyper-remnantaemia is dependent on both the nature of the meal fatty acids ingested and possible metabolic determinants that influence chylomicron metabolism. The study findings reiterate that fasting plasma TAG is a poor indicator of atherogenic chylomicron remnant homoeostasis and emphasises the merits of considering specifically, chylomicron remnant abundance and kinetics in the context of atherogenic risk. Few studies address the latter, despite the majority of life being spent in the postprandial and absorptive state.

Abstract Background: The measurement of triglyceride (TG)-rich particles after an oral fat challenge has been used to provide a measure of risk for coronary artery disease independent of the fasting plasma triglyceride concentration. The analytical “gold standard” for measuring TG-rich lipoproteins uses density gradient ultracentrifugation; however, this technique is labor-intensive. Because of our need to perform numerous postprandial analyses of TG-rich lipoproteins for a large interventional study (Genetics of Lipid Lowering Drugs and Diet Network), we evaluated the use of nuclear magnetic resonance (NMR) spectroscopy for measuring TG-rich particles. Methods: EDTA-blood samples were obtained 0, 3.5, 6, and 8 h after ingestion of an oral fat meal (89% of calories from fat) in 20 apparently healthy individuals. The plasma TG concentrations of chylomicron and chylomicron remnant/VLDL fractions were analyzed by ultracentrifugation and NMR spectroscopy. Results: Comparison of all values (n = 78) by ultracentrifugation (x) and NMR (y) produced a linear regression equation of y = 0.979x − 0.035 mmol/L (R2 = 0.90) for chylomicrons and y = 1.398x + 0.067 mmol/L (R2 = 0.96) for the fraction containing chylomicron remnants and VLDL. Postprandial response of chylomicrons and chylomicron remnant/VLDL was similar, with maximum response occurring between 3.5 to 6 h regardless of method of measurement. Conclusion: Chylomicron and chylomicron remnant/VLDL fraction measurements obtained by NMR have a high degree of correlation with results produced by ultracentrifugation. NMR may therefore be suitable as an alternative method for the measurement of postprandial TG-rich lipoproteins in individuals consuming a high-fat meal.

The uptake in vivo of chylomicrons and beta-migrating very-low-density lipoprotein (beta-VLDL) by rat liver, which is primarily carried out by parenchymal cells, is inhibited, 5 min after injection, to respectively 35 and 8% of the control values after preinjection of lactoferrin. The decrease in the uptake of lipoproteins by the liver caused by lactoferrin is a specific inhibition of uptake by parenchymal cells. Competition studies in vitro demonstrate that chylomicron remnants and beta-VLDL compete for the same recognition site on parenchymal cells. Data obtained in vivo together with the competition studies performed in vitro indicate that chylomicron remnants and beta-VLDL interact specifically with the same remnant receptor. Hepatic uptake of 125I-labelled-alpha 2-macroglobulin in vivo, mediated equally by parenchymal and endothelial cells, is not decreased by preinjection of lactoferrin and no effect on the parenchymal-cell-mediated uptake is found. In vitro, alpha 2-macroglobulin and chylomicron remnants or beta-VLDL show no cross-competition. Culturing of parenchymal cells for 24-48 h leads to a decrease in the cell association of alpha 2-macroglobulin to 26% of the initial value, while the cell association of beta-VLDL with the remnant receptor is not influenced. It is concluded that beta-VLDL and chylomicron remnants are recognized by a specific remnant receptor on parenchymal liver cells, while uptake of alpha 2-macroglobulin by liver is carried out by a specific receptor system (presumably involving the LDL-receptor-related protein) which shows properties that are distinct from those of the remnant receptor.

The lipids extracted from chylomicrons, chylomicron remnants generated in vivo and hepatic-lipase-treated chylomicrons were emulsified by sonication. These emulsified particles retained the capacity of the native lipoproteins to be differentiated by the liver in vivo, i.e. only the particles derived from remnant and hepatic-lipase-treated chylomicron lipids were efficiently taken up by the liver. To investigate the role of phospholipids in this differentiation process, the phospholipids of all three lipoprotein preparations were separated from the remaining lipids by silicic acid chromatography. The phospholipid-free lipid fraction of chylomicrons was then emulsified with the phospholipids derived from each of the three lipoprotein preparations. Only the particles emulsified with phospholipids derived from remnants and hepatic-lipase-treated chylomicrons were efficiently taken up by the liver in vivo. These results support the proposition that phospholipids modulate the hepatic differentiation between chylomicrons and remnants in vivo.

The binding and uptake of chylomicron remnants by human macrophages was studied in order to resolve paradoxical observations that have described the putative mechanisms by which postprandial lipoproteins induce foam cell formation. Chylomicron remnants bound to human monocyte-derived macrophages (HMMs) and to the transformed monocytic cell line THP-1 with high affinity (Kd of approx. 5.5 µg of chylomicron remnant protein/ml). Binding was found to be saturable for both cell types, and was strongly inhibited in the presence of unlabelled chylomicron remnants. Ligand blot studies with colloidal-gold-labelled chylomicron remnants identified two cell surface binding sites on both HMMs and THP-1 cells, with molecular masses of approx. 128 kDa and 43 kDa. The high-molecular-mass binding site was found to be the low-density lipoprotein (LDL) receptor, based on the strong inhibition of chylomicron remnant binding in the presence of unlabelled LDL, Fab2 antibody fragments to the LDL receptor or calcium chelators. Competition studies suggested that, in HMMs, the LDL receptor appeared to facilitate approximately half of the total chylomicron remnant uptake. In contrast, the LDL receptor was not significantly involved in macrophage uptake of chylomicron remnants by THP-1 cells. The identity of the 43 kDa binding site is presently unknown, but, importantly, expression was not inhibited as a consequence of sterol loading, which was induced by incubating HMMs and THP-1 cells with 25-hydroxycholesterol. In contrast, the expression of the LDL receptor was substantially attenuated following lipid loading. Collectively, our data suggest that, while the macrophage LDL receptor can bind chylomicron remnants and facilitate uptake in non-lipid-loaded HMMs, other sterol-insensitive sites are responsible for the unabated uptake of chylomicron remnants by macrophages. We propose that the 43 kDa macrophage chylomicron remnant binding protein may be a candidate for the sterol loading of macrophages.

[Formulae and special characters can only be approximated here. Please see the pdf version of the abstract for an accurate reproduction.] Atherosclerosis is a common degenerative disease in which the clinical manifestations are often through stroke or myocardial infarction. Some of the established risk factors for atherosclerosis include elevated plasma low-density lipoprotein (LDL)-cholesterol levels, obesity, diabetes mellitus (DM) and cigarette smoking. Of the risk factors, an elevation in plasma LDL is one of the most established and the most researched. This is partly a consequence of the deposition of cholesterol within arterial intima being a crucial step in the progression of atherosclerosis, combined with the finding that LDL particles are a major transporter of cholesterol in circulation. Recently there is increasing evidence showing a role of the other major transporter of cholesterol in circulation, chylomicron remnants, in the progression of atherosclerosis. The notion of atherosclerosis as a postprandial phenomenon has been further substantiated by the emergence of evidence showing a direct role of chylomicron remnants in arterial cholesterol deposition. Based on evidence that chylomicron remnants are proatherogenic, the suggestion arises that accumulation of postprandial lipoproteins in plasma may add another dimension of risk to the development of coronary artery disease (CAD). This thesis tests the general hypothesis that individuals with or at high risk of CAD have postprandial dyslipidaemia and that this metabolic abnormality is correctable with a class of lipid-lowering drugs called statins. To test the hypothesis, clinical studies were conducted in normolipidaemic CAD patients, heterozygous familial hypercholesterolaemia (FH) and postmenopausal women with type 2 DM. Determination of postprandial dyslipidaemia by comparison with control populations were conducted initially in each patient group (Studies 1, 3 and 5), followed by intervention studies investigating possible modulation of the dyslipidaemia with a statin (Studies 2, 4 and 6). Six observation statements based on case-control comparisons of postprandial lipaemia in patients with or at risk of CAD and the effects of statins on postprandial dyslipidaemia in the patient groups were derived from the general hypothesis. The observation statements were examined in the individual studies described below. Postprandial lipoprotein metabolism was assessed using a number of methods. For comparison of postprandial lipaemia in Studies 1 and 2, a classic oral fat challenge was utilised. As markers of chylomicrons and chylomicron remnants, retinyl palmitate and triglyceride were measured postprandially as well as apolipoprotein (apo) B48 concentrations, a specific marker of intestinal lipoproteins. ApoB48 was also measured in the fasting state and found to predict the postprandial responses of retinyl palmitate, triglyceride and apoB48. This suggested that fasting measurement of apoB48 could be used as a simple indicator of postprandial dyslipidaemia. Consequently for Studies 3 - 6, fasting apoB48 measurements were used as primary markers of postprandial dyslipidaemia. Other markers for chylomicrons and their remnants utilised were fasting plasma concentrations of remnant-like particle-cholesterol (RLP-C) and apoC-III. As well as these static markers, chylomicron remnant catabolism was measured using a stable isotope breath test. The breath test involves the intravenous injection of a chylomicron remnant-like emulsion labelled with ¹³C-oleate and measurement of enriched ¹³CO2 in expired breath by isotope ratio mass spectrometry. The fractional catabolic rate (FCR) of the injected emulsion was subsequently calculated using multi-compartmental modeling (SAAM II). The studies are presented in this thesis as published and unpublished works. In Study 1, postprandial lipoprotein metabolism was compared between 18 normolipidaemic CAD patients (cholesterol 4.54 ± 0.12 mmol/L, triglyceride 1.09 ± 0.16) with 13 asymptomatic healthy controls using an oral fat challenge. Normolipidaemic CAD patients had higher postprandial area-under-curve (AUC) for triglyceride (+34%, p=0.019), retinyl palmitate (+74%, p=0.032) and apoB48 (+36%, p<0.001). Fasting apoB48 was also higher (+41%, p=0.001) and found to correlate significantly with AUC of triglyceride (p=0.017), retinyl palmitate (p=0.001) and apoB48 (p<0.001). The data suggest that normolipidaemic CAD patients have increased concentrations of intestinal lipoproteins in the fasting and postprandial state. In addition to these findings, significant correlations of fasting apoB48 with postprandial markers (p<0.02) suggests the fasting marker to be a simpler surrogate marker for the degree of total postprandial lipaemia. Study 2 investigated the effect of atorvastatin treatment on postprandial dyslipidaemia found in the 18 near-normolipidaemic CAD patients from Study 1. The trial was conducted in a randomised, placebo-controlled design, using oral fat challenges before and after 12-weeks atorvastatin/placebo treatment. Compared with the placebo group, atorvastatin decreased the total postprandial AUC for iii triglyceride (-22%, p=0.05) and apoB48 (-34%, p=0.013). Fasting markers of apoB48 (-35%, p=0.019) and RLP-C (-36%, p=0.032) also decreased significantly. Atorvastatin was also found to increase LDL-receptor activity by +218% (p<0.001) as reflected in binding studies. The data suggest atorvastatin reduces the fasting levels of intestinal lipoproteins as well as total postprandial lipaemia, but without acute dynamic changes in postprandial lipaemia. The reduction in fasting and total postprandial lipoprotein levels could be partly attributed to an increase in LDL-receptor mediated removal from circulation. In Study 3, postprandial lipaemia was compared in 15 heterozygous FH patients with 15 healthy controls. FH patients had higher fasting concentrations of apoB48 (+56%, p<0.001) and RLP-C (+48%, p=0.003). The elevation in these fasting markers of chylomicrons and their remnants suggests FH patients have postprandial dyslipidaemia due to an accumulation of these particles in plasma. Study 4 examined the effects of long- (> 6 months) and short-term (4 weeks) simvastatin treatment on modulating postprandial dyslipidaemia found in the 15 FH patients from Study 3. Short- and long-term simvastatin treatment decreased the fasting concentrations of apoB48 (-29% and 15% respectively, p<0.05) and RLP-C (both -38%, p<0.001), but did not significantly alter the FCR of the injected chylomicron remnant-like emulsion. The data suggest that in heterozygous FH both long- and short-term simvastatin treatments decrease the fasting markers of postprandial lipoproteins by mechanisms that may not be mediated via processes differentiated by the 13CO2 breath test. This implies that the effect on postprandial lipaemia may be from a decrease in production and/or a possible increase in catabolism of triglyceride-rich lipoproteins (TRLs). In Study 5, postprandial lipaemia was compared in 24 postmenopausal women age and body mass index matched with 14 postmenopausal women with type 2 DM. Postmenopausal diabetic women were found to have higher fasting concentrations of apoB48 (+21%, p=0.021) and apoC-III (+16%, p=0.042) as well as lower FCR of the chylomicron remnant-like emulsion (-50%, p<0.001). The data suggest that postmenopausal diabetic women have postprandial dyslipidaemia, and that this is due to delayed catabolism of chylomicron remnants. Study 6 was an hypothesis-generating exercise examining the effects of 4-weeks pravastatin treatment on postprandial dyslipidaemia found in 7 postmenopausal women with type 2 DM from Study 5. Although plasma LDL-cholesterol was reduced (-19%, p=0.028), there were no significant effects found on fasting apoB48 concentrations (-12%, p=0.116) or the FCR of the chylomicron remnant-like emulsion (+38%, p=0.345). A larger sample size of patients and/or treatment with a more potent statin at a dosage known to affect chylomicron remnant metabolism would be required to demonstrate a significant reduction in postprandial dyslipidaemia in postmenopausal women with type 2 DM. The results of the above mentioned studies combined support the general hypothesis that postprandial dyslipidaemia is a feature of patients with or at risk of CAD. This defect may be demonstrated using fasting apoB48 as an indicator of the degree of postprandial lipaemia. Postprandial dyslipidaemia may reflect a reduction in catabolism, as suggested with the breath test in type 2 DM, and/or an over overproduction of chylomicrons. Both these mechanisms would also increase competition for lipolysis and clearance pathways between hepatically and intestinally-derived lipoproteins. The exact mechanisms by which postprandial dyslipidaemia occurs are yet to be determined. Statins appear to improve defective postprandial lipaemia in patients with or at risk of CAD, which is in agreement with the general hypothesis. The effectiveness of a statin is dependant on their potency in inhibiting cholesterol biosynthesis and increasing receptor mediated clearance of LDL and chylomicron remnants. The studies conducted in this thesis show that postprandial dyslipidaemia can be reduced by statins but not to the extent demonstrated in controls. However, the demonstrated reduction in fasting and total postprandial lipaemia translates to a lowering in overall arterial exposure to circulating proatherogenic particles. The elevation in fasting and postprandial levels of proatherogenic chylomicron remnants found in the patient groups described in this thesis indicates another dimension to their risk of coronary disease. The reductions in the overall levels of proatherogenic particles in patients with or at high CAD risk, infers a possible reduction in the risk of coronary disease in these patients.

Dietas vegetarianas oferecem baixo conteúdo calórico, baixos níveis de gordura saturada, colesterol, proteína animal e mais altos de gordura polinsaturada, carboidratos, fibras, magnésio, boro, folato e antioxidantes. Todos esses nutrientes influenciam nos fatores de risco de doenças cardiovasculares como hipertensão arterial, diabetes mellitus, obesidade e dislipidemias. Níveis plasmáticos de colesterol total, colesterol de lipoproteína de baixa densidade (LDL), de lipoproteína de densidade muito baixa (VLDL) e triglicérides em indivíduos vegetarianos são menores, em vários estudos, quando comparados a indivíduos onívoros. O metabolismo de quilomícrons (Qm) e dos seus produtos de degradação pela lipase lipoprotéica, os remanescentes, lipoproteínas que transportam os lípides da dieta na circulação sanguínea, não foi avaliado até o momento e está relacionado à aterosclerose. O objetivo deste estudo foi avaliar a cinética plasmática de quilomícrons artificiais marcados com triglicérides (TG-3H) e éster de colesterol (EC-14C) e aspectos qualitativos da HDL, em 18 indivíduos ovolacto-vegetarianos (excluem da alimentação carne, frango e peixe), 21 indivíduos veganos (não consomem nenhum alimento de origem animal), há pelo menos 5 anos e 29 indivíduos onívoros (consomem alimentos de origem animal), todos normolipidêmicos, não diabéticos e sem uso de medicamentos hipolipemiantes. Após a injeção endovenosa dos Qm artificias, foram colhidas amostras de sangue em tempos pré-estabelecidos durante 60 minutos. A radioatividade em cada uma das amostras foi medida para o cálculo da taxa fracional de remoção (TFR) dos lípides radioativos, através de análise compartimental. Foram realizadas as determinações bioquímicas nesses indivíduos e calculada a atividade da lipase lipoprotéica pós-heparina, em ensaio in vitro. Verificou-se também a transferência de lípides de uma nanoemulsão lipídica para a lipoproteína de alta densidade (HDL) e o diâmetro dessa lipoproteína. A remoção plasmática dos remanescentes de quilomícrons avaliada pela taxa fracional de remoção do éster de colesterol da emulsão, foi maior nos veganos (p<0,05) e ovolacto-vegetarianos (p<0,05) comparando-se aos onívoros, enquanto que o processo de lipólise dos quilomícrons, avaliado pela taxa fracional de remoção dos triglicérides da emulsão e pela medida da atividade da lipase lipoprotéica in vitro foi similar nos três grupos avaliados. Não foram encontradas diferenças significativas nas concentrações plasmáticas de HDLC, VLDL e triglicérides entre os grupos estudados .No grupo vegano, as concentrações plasmáticas de LDL-C e glicose foram menores quando comparadas apenas ao grupo dos onívoros (p<0,05, p<0,01; respectivamente). Já em relação ao colesterol total, os indivíduos veganos apresentaram menores níveis quando comparados tanto aos ovolacto-vegetarianos (p<0,05) como aos onívoros (p<0,01). Não observou-se diferença na transferência de lípides da nanoemulsão para a HDL e no tamanho da HDL entre os três grupos. Os resultados do presente estudo sugerem que a dieta vegana e ovolacto-vegetariana aceleram a remoção dos remanescentes de quilomícrons, lipoproteínas aterogênicas, o que pode estar relacionado, aos efeitos benéficos dessa dieta em relação a doenças em relação ao processo aterosclerótico
Vegetarian diets provide less caloric content, low levels of saturated fats, cholesterol and animal protein while providing at the same time providing high levels of polyunsaturated fats, carbohydrates, fibers, magnesium, borium, folate and antioxidants. All these nutrients have an influence upon the cardiovascular diseases such as hypertension, diabetes mellitus, obesity and dyslipidemias. Studies have shown that total cholesterol plasmatic levels, low density lipoprotein (LDL), very low density lipoprotein (VLDL) and triglycerides in vegetarian individuals are lower when compared to omnivores individuals. Chylomicron metabolism (Qm) and its lipoprotein lipase degradation products, the remnants, lipoproteins that transport dietary lipids in the blood has not yet been evaluated, although it is related to atherosclerosis. This study evaluated the plasmatic kinetics of artificial chylomicrons marked with triglycerides (3HTG) and cholesterol esters (14C-CE), as well as the qualitative aspects of HDL in 13 ovolacto-vegetarians (no ingestion of meat, chicken or fish), 10 vegan individuals (no ingestion of any food of animal origin) for more than 5 years and 14 omnivores individuals (ingestion of animal origin foods). All participants were normolipidemic, non diabetic and using no hypolipemiants medication. After an intravenous injection containing artificial Qms, blood samples were collected during 60 minutes at predetermined times. The radioactivity of each sample was measured and the fractional clearance rate (FCR) calculated for the radioactive lipids using compartmental analysis. Biochemical determinations were undertaken in order to calculate the post-heparin lipoprotein lipase activity in vitro. Also evaluated were the lipid transfer of the lipid nanoemulsion to the HDL and the diameter of the HDL particles. The plasma removal of the chylomicron remnants evaluated by the fractional clearance rate of the cholesteryl ester of the emulsion was greater in the vegan (p<0,05) and ovolacto-vegetarian (p<0,05) groups when compared to the omnivore group. The lipolysis of the chylomicron evaluated by the fractional clearance rate of the emulsion triglycerides and by the in vitro lipoprotein lipase activity assay was similar in the three studied groups. There were no differences in the plasma concentrations of HDL-C, VLDL-C and triglycerides between the three groups. The plasma concentrations of LDL-C and glucose of the vegan group were lower than omnivore group (p<0.05 and p<0.01, respectively). In regards to total cholesterol, vegans present lower levels when compared to both ovolactovegetarians (p<0.05) and omnivores (p<0.01). No difference was found in the transfer of nanoemulsion lipids to HDL or in the size of the HDL of all three groups. These results suggest that the vegetarian diet can improve the metabolism of chylomicron remnants, atherogenic lipoproteins, which can be related to the beneficial effects of this diet upon the atherosclerosis process.

Thesis (M.A.)--Boston University
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The low-density lipoprotein receptor-related protein (LRP) is a 4544 amino acid polypeptide with structural similarity to the low-density lipoprotein receptor. LRP contains two subunits, a 515kDa subunit and an 85kDa subunit. LRP is found in a wide range of tissues, although its main function is confined to the liver. LRP is an Apo E binding receptor, which led to the idea that it might serve to clear chylomicron remnants and large Beta-VLDL from the plasma. The majority of research supports this hypothesis, although a small amount of conflicting data exists that will require further explanation. LRP has also been implicated as a receptor for alpha2-macroglobulins, which are protease inhibitors present in the plasma. Therefore, it appears that LRP and the alpha2-macroglobulin receptor are the same molecule.
2031-01-01

Dietary-derived lipoproteins, chylomicrons (CM) and CM remnants (CMR), have been implicated in the progression of cardiovascular disease. Retinyl esters are currently the most widely used method for monitoring CM metabolism. The availability, however, of a specific antisera to apo B-48, the protein uniquely associated with dietary-derived lipoproteins, has allowed more extensive investigation of CM and CMR metabolism. The effect of habitual, moderate levels of exercise (3 to 4 exercise sessions a week) on the lipaemic response to meals of varying fat content was assessed in young male subjects. Apo B-48, triacylglycerol (TAG) and retinyl ester were used as markers for CM particles. Active subjects had a lower response than an inactive group in all parameters measured over time after the meals. Lipoprotein lipase (LPL) activity levels measured at the end of the postprandial period were higher in the active group. The area under the time-response curves (AUC) for apo B-48 in the inactive group increased with increasing fat content of the meals, whereas the AUC for apo B-48 was the same after each meal in the active group. Validation of a specific ELISA for apo B-48 was carried out. Cross-reactivity of the antisera with low levels of apo B-100, the protein present on endogenous lipoproteins, was ruled out. The assay was specific and sensitive for measuring apo B-48 concentrations in the CM-enriched fractions. The use of the assay in the current format for plasma samples could not be fully assessed due to difficulties with isolating a pure, concentrated sample of apo B-100 and problems with reactivity between the secondary antibody used in the assay and plasma proteins. The assay was useful for showing postprandial patterns of changes in apo B-48 levels in plasma. The effects of meal frequency on the lipaemic response to a high fat test meal challenge were assessed in an intervention study. A nibbling diet was found to cause differences between the response of various parameters after the meal (NEFA-AUC, LPL activity, infranatant-TAG AUC and time to peak) compared with the normal meal frequency. The size and density distribution of CMR in plasma were investigated. Apo B-48 was found in the IDL and LDL fractions in both the postabsorptive and postprandial states. A comparison between the retinyl ester and apo B-48 responses in the postprandial studies showed that the time to peak retinyl ester level was delayed compared to apo B-48 and TAG. The importance of apo B-48 for studying the metabolism of CM and CMR metabolism was demonstrated.

Lipids are carried in plasma as microparticles, lipoproteins, composed of a core of hydrophobic lipids and a surface of amphipathic lipids. In addition, the particles carry proteins (i.e. apolipoproteins). The proteins have key functions in the metabolism as receptor ligands, enzymes or activators. Lipoproteins are classified based on density into: chylomicrons, VLDL, IDL, LDL, and HDL. Retention of apoB-containing lipoproteins (LDL, IDL, and VLDL) in the arterial intima is the initiating event in the development of atherosclerosis. Retention is mediated by binding of apoB to structural proteoglycans in the intima. Increased plasma concentration of apoB-containing lipoproteins is the main risk factor for atherosclerotic cardiovascular disease (CVD) and the causative role of LDL has been demonstrated in several studies. Lp(a) is a subclass of LDL and elevated Lp(a) is an independent risk-factor, primarily genetically mediated. Genetic data support that high Lp(a) causes atherosclerosis. Elevated triglycerides in plasma are associated with increased risk for CVD. Whether triglycerides directly induce atherogenesis is still unclear, but current data strongly support that remnant particles from triglyceride-rich lipoproteins are causal. HDL are lipoproteins that have been considered to be important for reversed cholesterol transport. Low HDL is a strong risk-factor for CVD. However, the causative role of HDL is debated and intervention studies to raise HDL have not been successful. Reduction of LDL is the main target for prevention and treatment, using drugs that inhibit the enzyme HMG-CoA reductase, i.e. statins. Other drugs for LDL reduction and to modify other lipoproteins may further reduce risk, and new therapeutic targets are explored.