Disturbances in dietary fat metabolism and their role in the development of atherosclerosis (original) (raw)
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The British journal of nutrition, 2017
TAG 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. H...
Atherosclerosis, 2002
In animal model studies, the uptake of chylomicron remnants after entering in the space of Disse occurs mainly by low-density lipoprotein (LDL) receptor and LDL receptor-related protein (LRP). In subjects, the relative importance of each one of these receptors for the clearance of chylomicron remnants is not fully understood. In our study, LDL cholesterol and apolipoprotein (apo) B were correlated to the plasma kinetics of a chylomicron-like emulsion in 77 subjects (11 women, mean age 58 9 12 years) with coronary artery disease (CAD). Their total cholesterol was 227 9 25 mg/dl, triglyceride 159 925 mg/dl, LDL cholesterol 148927 mg/dl, HDL cholesterol 40 99 mg/dl, apo A1 1.8090.53 g/l and apo B 1.65 9 0.48 g/l. The emulsion was double-labeled with 3 H-triolein and 14 C-cholesteryl oleate and injected intravenously after 12-h fasting. The decay curves of the radioisotopes were determined from blood samples collected at predetermined intervals during 60 min. A negative correlation between FCR of the emulsion cholesterol esters and LDL cholesterol and apo B plasma concentrations was found (r= −0.4, P= 0.005 and r= −0.3, P =0.01, respectively) whereas FCR of the emulsion triglycerides did not correlate with any of the plasma lipids or apolipoprotein parameters. Concluding, in patients with CAD, LDL catabolic pathway significantly influences the removal from plasma of chylomicron remnants.
High cholesterol intake modifies chylomicron metabolism in normolipidemic young men
The Journal of nutrition, 2006
Whether the consumption of egg yolk, which has a very high cholesterol content without excess saturated fats, has deleterious effects on lipid metabolism is controversial. Absorbed dietary cholesterol enters the bloodstream as chylomicrons, but the effects of regular consumption of large amounts of cholesterol on the metabolism of this lipoprotein have not been explored even though the accumulation of chylomicron remnants is associated with coronary artery disease (CAD). We investigated the effects of high dietary cholesterol on chylomicron metabolism in normolipidemic, healthy young men. The plasma kinetics of a chylomicron-like emulsion, doubly-labeled with 14C-cholesteryl ester (14C-CE) and 3H-triolein (3H-TG) were assessed in 25 men (17-22 y old, BMI 24.1 +/- 3.4 kg/m2). One group (n = 13) consumed 174 +/- 41 mg cholesterol/d and no egg yolk. The other group (n = 12) consumed 3 whole eggs/d for a total cholesterol intake of 804 +/- 40 mg/d. The nutritional composition of diets w...
Atherosclerosis, 1996
Association of apo(a)/Lp(a) with triglyceride-rich lipoproteins (TGR-Lps) is determined by different factors that are poorly understood. Some previous studies suggested that ape(a) in TGR-Lps may affect the atherogenicity of the TGR particles. To study whether there are any peculiarities in postprandial (pp) Lp(a) metabolism, we have determined ape(a) phenotypes and Lp(a) concentrations in 46 subjects with coronary heart disease (CHD) and in six normolipidemic individuals at different time points (4, 6 and 8 h) following an oral fat tolerance test. While mean triglyceride concentration reached its maximum 6 h after a standardized fat meal, no change in total cholesterol and in mean Lp(a) plasma concentration was detected at any time point after the fat load. In 6 normolipidemic probands and in 8 patients with CHD, who were matched for ape(a) phenotype, lipoprotein levels, age and body weight, we followed the distribution of ape(a) in plasma density gradient fractions in the fasting and pp state. In the CHD patients a significant larger percentage of ape(a) reactivity was detected in TGR-Lps in the pre-as well as in the postprandial state, compared to control subjects. The fat intake did not induce a significant change of ape(a) reactivity in the TGR-Lp fractions in both groups. The ape(a) isoform-size and the Lp(a) plasma concentration in the fasting state had no influence on the individual variation of the Lp(a) concentration in pp TGR-Lp fractions. Our results provide evidence that TGR-Lp fractions of CHD patients are enriched in ape(a) reactivity compared to healthy controls, but do not support the hypothesis that Lp(a) acts atherogenically through a pp increase of its plasma concentration.
Circulation, 2000
Background —Exaggerated postprandial triglyceridemia is common in normolipidemic patients with coronary artery disease (CAD). Alterations in the composition of triglyceride-rich lipoproteins (TRLs) are likely to underlie this metabolic disturbance. However, the composition of very-low-density lipoproteins (VLDLs), which are the most abundant postprandial TRLs, has never been defined in CAD patients. Methods and Results —We examined postprandial changes in the number and composition of VLDLs in middle-aged, normolipidemic CAD patients and control subjects. TRLs from 14 patients and 14 control subjects aged 45 to 55 years were subfractionated by density gradient ultracentrifugation into Svedberg flotation rate (Sf) fractions >400, 60 to 400, and 20 to 60. The VLDLs were separated from chylomicron remnants by immunoaffinity chromatography. In CAD patients, the postprandial concentrations of triglycerides and large (Sf 60 to 400) VLDL particles were elevated. In addition, their postp...
Impaired chylomicron remnant clearance in familial combined hyperlipidemia
Arteriosclerosis and Thrombosis: A Journal of Vascular Biology, 1993
Postprandial chylomicron remnant clearance was studied in six patients with familial combined hyperlipidemia (FCH) and seven control subjects by using an oral retinyl palmitate (RP) fat-loading test. The chylomicron remnant clearance (Sf < 1,000 fraction), expressed as the area under the RP curve (AUC-RP), was delayed in FCH subjects (65.05 +/- 12.84 hours x [mg/L]) compared with control subjects (25.1 +/- 5.4 hours x [mg/L]; p = 0.01). Postprandial lipoprotein particle size and composition in the Sf > 1,000 fraction were different between FCH and control subjects as analyzed by molecular-sieve chromatography. Fasting high density lipoprotein cholesterol was lower in FCH patients (0.54 +/- 0.09 mmol/L) than in control subjects (0.89 +/- 0.05 mmol/L; p < 0.01). Mean plasma postheparin lipoprotein lipase and hepatic lipase activities were similar between FCH patients (94 +/- 25 and 427 +/- 57 milliunits/mL, respectively) and control subjects (126 +/- 16 and 362 +/- 33 milliun...
Atherosclerosis, 1980
In order to evaluate the relationship between triglyceride-rich lipoproteins (chylomicrons and VLDL) and HDL during alimentary lipaemia, 12 healthy volunteers, 6 male and 6 female (aged 20-40 yrs), were studied. Cholesterol, phospholipid, triglyceride and protein were evaluated in whole serum, VLDL, LDL and HDL (successively subfractionated in HDLz and HDL3). Blood samples were collected in a fasting state, 4.5 and 9 h after a 1500 calorie meal (20% protein, 40% carbohydrate, 40% fat). A striking increase in triglyceriderich lipoproteins after 4.5 h was observed in both sexes, but was more pronounced in males. An increase in phospholipid and triglyceride as well as a slight reduction in cholesterol was evident in HDL after 4.5 h. At the same time both lipids and proteins were decreased in HDL3 and 'increased in HDLz. This phenomenon is more evident in females, who showed a significantly higher basal HDLz level. These results suggest a possible metabolic relationship in the post-prandial phase between triglyceride-rich lipoproteins and HDL, and an inverse correlation between HDLz and HDL3.
European Journal of Clinical Investigation, 1986
Abstract. Type V hyperlipoproteinaemia is a disorder of lipid transport characterized by the accumulation in serum of chylomicrons and very low density lipoproteins. The purpose of the study was the analysis of serum lipids and lipoproteins by ultracentrifugation in nine patients with primary type V hyperlipoproteinaemia before and during dietary treatment. After 30 days of balanced isocaloric diet mean serum triglycerides fell from 25·4 ± 15·0 (mean ± SD) to 2·8 ± 1·7 mmol l-1. At the same time the chylomicrons and the very low density lipoproteins of flotation rate higher than 100 disappeared from the serum while the remaining very low density lipoproteins maintained unaltered their normal protein–lipid composition. After 30 days the low density lipoproteins increased significantly in concentration (from 1·6 ± 0·8 to 4·1 ± 1·1 mmol l-1 cholesterol) and their percentage content of cholesterol and triglyceride was increased and reduced, respectively. The highest concentration of intermediate density lipoprotein cholesterol was observed after 15 days of treatment (1·2 ± 0·6 mmol l-1). The abnormally low concentrations and the physico-chemical properties of the high density lipoproteins remained unchanged throughout the study (from 0·6 ± 0·2 to 0·8 ± 0·2 mmol l-1 cholesterol concentration) and no high density lipoproteins two (HDL2) were observed at any time. The effects of this treatment were an increase in low density and marginal change in high density lipoproteins which are considered, respectively, a positive and a negative risk factor for atherosclerosis.