Alimentary Lipemia Research Articles

A single high-fat meal provokes pathological erythrocyte remodeling and increases myeloperoxidase levels: implications for acute coronary syndrome

High-fat meal (HFM) consumption can produce acute lipemia and trigger myocardial infarction in patients with atherosclerosis, but the mechanisms are poorly understood. Erythrocytes (red blood cells, RBCs) intimately interact with inflammatory cells and blood vessels and play a complex role in regulating vascular function. Chronic high-fat feeding in mice induces pathological RBC remodeling, suggesting a novel link between HFM, RBCs, and vascular dysfunction. However, whether acute HFM can induce RBC remodeling in humans is unknown. Ten healthy individuals were subjected to biochemical testing and assessment of endothelial-dependent flow-mediated dilation (FMD) before and after a single HFM or iso-caloric meal (ICM). Following the HFM, triglyceride, cholesterol, and free fatty acid levels were all significantly increased, in conjunction with impaired post-prandial FMD. Additionally, peripheral blood smears demonstrated microcytes, remodeled RBCs, and fatty monocytes. Increased intracellular ROS and nitration of protein band 3 was detected in RBCs following the HFM. The HFM elevated plasma and RBC-bound myeloperoxidase (MPO), which was associated with impaired FMD and oxidation of HDL. Monocytic cells exposed to lipid in vitro released MPO, while porcine coronary arteries exposed to fatty acids ex vivo took up MPO. We demonstrate in humans that a single HFM induces pathological RBC remodeling and concurrently elevates MPO, which can potentially enter the blood vessel wall to trigger oxidative stress and destabilize vulnerable plaques. These novel findings may have implications for the short-term risk of HFM consumption and alimentary lipemia in patients with atherosclerosis.A single high fat meal can induce pathological red blood cell (RBC) remodeling and oxidative stress, in conjunction with elevations in plasma, RBC-bound myeloperoxidase (MPO) and MPO-mediated high-density lipoprotein oxidation. These findings demonstrate that consumption of heavy meals enriched in fat may promote destabilization of vulnerable plaques leading to acute myocardial infarction.

Goutweed (Aegopodium podagraria L.) biological activity and the possibilities of its use for the correction of the lipid metabolism disorders

The article summarizes data concerning the biological activity of the promising herbal raw material: aerial part of goutweed (Aegopodium podagraria L., Apiaceae). This plant since time immemorial has been used as vegetable and fodder plant as well as in folk medicine including the treatment of the metabolic disorders. Nowadays the interest in this plant increases. The technology of obtaining the extract and the tincture from goutweed aerial part is described, the chemical composition of these preparations is elucidated. Pharmacological effects of the preparations obtained from goutweed are characterized with the special emphasis on the possibilities of the lipid metabolism disorders correction and prevention. The presented experimental results substantiate the efficacy of goutweed extract and the tincture under the conditions of alimentary lipemia together with their safety in the intact animals. Thus, the hypolipidemic activity of goutweed extract (1 g/kg intragastrically) and goutweed tincture (1 cm3/kg intragastrically) was shown in the test with olive oil loading in rats. The extract appeared to be able to decrease significantly the level of triglycerides in blood plasma, while the tincture reduced the content of plasma total lipids. In the intact rats, the extract at doses of 100 mg/kg and 1 g/kg as well as the tincture at doses of 1 and 5 cm3/kg did not influence on the values of the lipid metabolism after 12 days of administration. Total and HDL cholesterol as well as atherogenic index and plasma total lipids level remained unchanged. In contast to the data previously obtained on the models of hyperuricemia, in the intact rats there were no changes in plasma uric acid concentration (which was determined proceeding from the role of the purine metabolism disorders in metabolic syndrome pathogenesis). Thus, goutweed preparations are characterized with the regulatory mode of action and sufficient level of safety. The development of drugs as well as functional foods containing goutweed herbal raw material is promising.

Update on genetics of postprandial lipemia

The relationship between alimentary lipemia and coronary disease is of great interest in view of the epidemiological and experimental evidence that underlies it. The modulation of such phenomena is influenced by both genetic and environmental factors, thus explaining their extraordinary individual variance. Over the last two decades there has been an explosion of research in this area, with often conflicting findings reported in the literature. In this study we have presented the current evidence linking a number of candidate genes ( APOA1/C3/A4/A5 cluster, ABCA1, CETP, GCKR, HL, IL-6, LPL, PLIN, and TCF7L2) to the modulation of the postprandial lipid metabolism. Increased knowledge of how these and other genes influence postprandial response should increase the understanding of personalised nutrition.

Correlation of serum IGF‐I and IGFBP‐1 and ‐3 to cardiovascular risk indicators and early carotid atherosclerosis in healthy middle‐aged men

IGF-I, IGFBP-1 and IGFBP-3 are putative mediators in cardiovascular disease. The present study examined (i) the correlations of circulating IGF-I, IGFBP-1 and IGFBP-3 to established cardiovascular risk factors and signs of early atherosclerosis as reflected by ultrasound measurement of common carotid intima-media thickness (IMT), and (ii) whether serum concentrations of these analytes are modulated during alimentary lipaemia. Cross-sectional clinical study. A biobank and clinical database based on 96 healthy Caucasian men, aged 50 years, with an apolipoprotein (apo) E3/E3 genotype, who had originally undergone investigations of postprandial lipoprotein metabolism was used for the study. Total IGF-I, IGFBP-1 and IGFBP-3 were determined in serum by radioimmunoassay (RIA). Free IGF-I was measured by a commercial two-site immunoradiometric assay (IRMA). In multivariate analyses, fasting serum free IGF-I correlated inversely with IMT and accounted for 5% of the variation in multiple R(2). When fasting serum IGFBP-1 was entered in the models instead of IGF-I, IGFBP-1 correlated positively with IMT and accounted for 6% of the variation in IMT. IGFBP-3 and total IGF-I were unrelated to IMT. There were no associations between free IGF-I and cardiovascular risk factors, whereas IGFBP-1 behaved like a component of the insulin resistance syndrome. Serum free IGF-I increased and IGFBP-1 decreased postprandially. The data indicate that serum free IGF-I and IGFBP-1 are implicated in early atherosclerosis.

Alimentary hyperlipemia of rabbits is affected by exposure to low‐intensity pulsed magnetic fields

An experimental study was carried out in rabbits to investigate the effects of exposing rabbits to low-intensity pulsed magnetic fields (PMFs) on alimentary hyperlipemia. Thirty female white big ear rabbits were randomly divided into three groups. The normal group was fed with a standard chow diet and the other two groups (hyperlipid and magnetic) were fed with the chow diet supplemented with cholesterol, yolk powder and lard. The magnetic group was exposed to 15 Hz pulsed magnetic fields. After 8 weeks, levels of blood lipid and indices of hemorheology were examined. In addition, histomorphologic changes of hepatic and myocardial tissues were compared across the groups respectively. Compared with the hyperlipid group, hemorheology indices of the magnetic group reduced significantly from 12.80% to 38.05% (P < 0.01) indicating lower blood viscosity. Similarly, compared with the hyperlipid group, the levels of total cholesterol and triglycerides in the magnetic group decreased 40.52% and 52.42% (P < 0.01). On the contrary, high density lipoprotein (HDL) value obviously increased 66.67% (P < 0.01). Furthermore, compared with the control group, the values of triglycerides and HDL of the magnetic group did not show statistical differences (P > 0.05). The deposit of fatty material on the inner lining of thoracic aorta wall of the magnetic group was significantly lighter than that of the hyperlipid group. Numerous aggregation of lipoids emerged among myocardial myofibrils in the hyperlipid group, while no notable change was found in both the magnetic and control group. The results indicate that low-intensity PMFs could be helpful for the treatment of alimentary hyperlipemia.

Alimentary lipemia enhances procoagulatory effects of inflammation in patients with a history of acute myocardial infarction complicated by ventricular fibrillation

Introduction Acute myocardial infarction, often occurring postprandially, can be complicated by ventricular fibrillation. The role of acute alimentary lipemia and inflammation in the occurrence of ventricular arrhythmias in acute myocardial infarction has not been described yet. Methods and results Before and 2 h after consumption of a defined fatty meal, blood samples of 27 patients with a history of acute myocardial infarction (AMI) were incubated with lipopolysaccharide (LPS). In 10 patients, AMI was complicated by ventricular fibrillation (VF), in 17 patients, AMI occurred without VF. CD40-ligand and CD62P expression on platelets, tissue-factor binding on monocytes and platelet–monocyte aggregates were measured with flow cytometry. Soluble CD40-ligand plasma levels were measured with an ELISA. With the meal, serum triglyceride levels increased from 211.85 ± 94.60 mg/dl to 273.59 ± 122.52 mg/dl ( p = 0.0002). LPS stimulation before the meal showed a non-significant tendency to increase platelet–monocyte aggregates and tissue factor on monocytes in both patient groups. LPS stimulation in acute alimentary lipemia significantly increased tissue-factor expression on monocytes in both patient groups and platelet–monocyte aggregates in patients with VF. Baseline plasma levels of soluble CD40L did not differ significantly between both groups. Acute alimentary lipemia significantly decreased total plasma levels of sCD40L, leading to a significantly lower level of sCD40L in patients with a history of VF. Conclusions Alimentary lipemia enhances procoagulatory effects of inflammatory stimulation in patients with a history of AMI complicated by ventricular fibrillation. These observations might reveal a mechanism for an increased risk of VF in acute coronary syndromes in a postprandial state.

High postprandial triglyceridemia in patients with type 2 diabetes and microalbuminuria

Microalbuminuria (MA) is an independent risk factor for atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Postprandial lipemia is also associated with excess cardiovascular risk. However, the association between MA and postprandial lipemia in diabetes has not been investigated. A total of 64 patients with T2DM, 30 with and 34 without MA, were examined. Plasma total triglycerides (TGs), triglycerides contained in chylomicrons (CM-TG), and TGs in CM-deficient plasma were measured at baseline and every 2 h for 6 h after a mixed meal. Postheparin LPL and HL activities were also determined. Plasma levels of apolipoprotein A-V (apoA-V), apoC-II, and apoC-III were measured in the fasting state and 2 h postprandially. Patients with MA had higher postprandial total TG levels than those without MA (P < 0.001); this increase been attributed mainly to CM-TG. LPL activity and fasting concentrations of the measured apolipoproteins were not different between the studied groups, whereas HL activity was higher in the patients with MA. ApoC-II and apoC-III levels did not change postprandially in either study group, whereas apoA-V increased more in the patients with MA. These data demonstrate for the first time that MA is characterized by increased postprandial lipemia in patients with T2DM and may explain in part the excess cardiovascular risk in these patients.

Effects of alimentary lipemia and inflammation on platelet CD40-ligand

Introduction In patients with chronic hypercholesterolemia, the CD40–CD40L dyad is upregulated, contributing to the initiation and progression of atherosclerosis. Our aim was to describe the role of postprandial lipemia and inflammatory stimulation on platelet and monocyte activation and CD40-ligand (CD40L) levels. Methods and results Before and 2 h after consumption of a defined fatty meal, whole blood samples of 31 healthy subjects were incubated with endotoxin (LPS). CD40-ligand and CD62P expression on platelets, tissue-factor expression on monocytes and platelet-monocyte aggregates were measured with flow cytometry. Soluble CD40-ligand plasma levels were measured with an ELISA. After the meal, serum triglyceride levels increased from 137.6 ± 60.5 mg/dl to 201.5 ± 75.0 mg/dl. Expression of CD40L and CD62P on platelets and plasma levels of soluble CD40L were significantly decreased. No significant changes after the meal were observed concerning tissue factor expression on monocytes and platelet-monocyte aggregates. Addition of LPS showed no significant effect concerning CD40L or CD62P expression on platelets, whereas the amount of platelet-monocyte aggregates significantly increased under LPS stimulation after the fatty meal. Conclusions Acute alimenatry lipemia leads to a decreased expression of CD40L on platelets and a reduced plasma level of sCD40L, suggesting an increased turnover in the CD40L system. Condensed abstract Before and after a fatty meal, blood samples of 31 healthy subjects were incubated with LPS. After the meal, expression of CD40L and CD62P on platelets and plasma levels of soluble CD40L were significantly decreased. Addition of LPS showed no effect concerning CD40L or CD62P expression, whereas the amount of platelet-monocyte aggregates significantly increased under LPS stimulation after the fatty meal.

Impact of postprandial lipaemia on low‐density lipoprotein (LDL) size and oxidized LDL in patients with coronary artery disease

Remnant lipoprotein particles (RLPs) and oxidative stress are components of postprandial state. We investigated the concentrations of triglyceride-rich lipoproteins (TRLs), RLPs, low-density lipoprotein (LDL) size, and oxidized LDL (oxLDL) during alimentary lipaemia, and evaluated whether changes among these variables could be associated with the severity and extent of coronary artery disease (CAD). Eighty men and 27 women with clinically suspected CAD underwent quantitative coronary angiography (QCA). TRLs were isolated by density gradient ultracentrifugation before and 6 h after an oral fat load. RLPs were measured by an immunoseparation method, oxLDL by ELISA, and LDL size by gradient gel electrophoresis. Triglycerides, apolipoprotein (apo) B-48, and apoB-100 concentration in Swedberg flotation units (Sf) > 400 and in Sf 12-400 fractions were markedly increased at 6 h. Postprandial cholesterol content of RLPs (RLP-C) correlated with respective triglycerides in Sf > 400 (r = 0.737) and Sf 12-400 (r = 0.857), apoB-48 in Sf > 400 (r = 0.710) and Sf 12-400 (r = 0.664), apoB-100 in Sf > 400 (r = 0.812) and Sf 12-400 (r = 0.533). RLP-C correlated with oxLDL both in fasting and in fed state (r = 0.482 and r = 0.543, respectively) and inversely with LDL size (r = -0.459 and r = -0.442, respectively). (P < 0.001 for all). OxLDL was elevated postprandially (P < 0.001). In multivariate analysis, oxLDL was a determinant of severity and extent of CAD. Postprandial state is associated with oxidative stress. The magnitude of oxLDL increases during alimentary lipaemia and is associated with coronary atherosclerosis.

Activation of coagulation during alimentary lipemia under real-life conditions

High intake of saturated fat is a predictor of coronary heart disease mortality. The phenomenon of postprandial angina pectoris has been described many years ago. Although earlier studies have demonstrated postprandial activation of coagulation factors VII and XII, platelets and monocytes, conclusive evidence for intravascular fibrin formation after a fat-rich meal has not been reported yet. The present study included 33 healthy physicians (7 females, 26 males) with a mean age of 42 years (range 27-62 years), and 27 coronary heart disease patients (8 females, 19 males) with a mean age of 63 years (range 47-81 years). Of the coronary heart disease patients, 26/27 were treated with acetylsalicylic acid and 25/27 with lipid-lowering drugs simvastatin or atorvastatin. Blood samples were drawn 30-60 min before and 30-60 min after a dinner consisting of rye bread with liversausage and black pudding as hors d'oeuvre, lettuce with smoked bacon in a lard dressing, stuffed fried goose with red cabbage, potato dumplings and sweet chestnuts, and white and brown mousse au chocolat. Average intake per person was 3760 kcal, with 125.9 g protein, 238.0 g fat and 268.9 g carbohydrate. We measured a significant postprandial increase in fibrinopeptide A (FpA) levels from 1.14+/-1.23 microg/l to 4.18+/-2.86 microg/l (p<0.0001) in healthy probands, and 4.66+/-13.61 microg/l to 12.80+/-15.04 microg/l (p<0.0001) in coronary heart disease patients. Triglycerides increased from 137.6+/-60.5 to 201.5+/-75.0 mg/dl in healthy probands and from 211.9+/-94.6 to 273.6+/-122.5 mg/dl in coronary heart disease patients. Fat-rich meals may cause procoagulant episodes, which may promote vascular complications such as myocardial infarction, transient ischemia attacks in susceptible persons.

Postprandial activation of hemostatic factors: Role of dietary fatty acids

Intake of dietary fat is an important determinant of the plasma concentration of triacylglycerol-rich lipoproteins, and the degree of alimentary lipemia is reported to have effects on hemostatic status including platelet function. Although association between the amount of dietary fat intake, lipemic response and certain cardiovascular disease (CVD) risk factors (VIIa and PAI-1) has been reported, the significance of the fatty acid composition of ingested fat for the postprandial lipid concentrations and the hemostatic factors is still unclear. Accumulating evidence suggests a relationship between dietary fatty acids and emerging hemostatic CVD risk factors, although much of this evidence is incomplete or conflicting. In order to improve our knowledge in this area, sufficient sample size in future studies are required to take into account of the genetic variation (gene polymorphisms for VII, PAI-1), sex, physical activity, stage of life factors, and sufficient duration to account for adaptation for definitive conclusions.

Postprandial changes in LDL phenotypes in patients with myocardial infarction

Low-density lipoprotein (LDL) particle size is strongly affected by both fasting and postprandial triglyceride levels. We report here that the LDL phenotype shifts toward the smaller phenotype during oral fat tolerance tests (OFTTs) in some patients with myocardial infarction (MI); a condition closely associated with postprandial increases of triglyceride and remnant-like particles (RLPs). Oral fat tolerance tests were performed on 63 MI patients with fasting serum triglyceride levels of less than 2.25 mmol L-1 (= 200 mg dL-1). Remnant-like particles and other serum lipids were compared among patients characterized by three LDL phenotypes based on nondenaturing gradient gel electrophoresis: pattern A (large LDLs, peak LDL particle size > or = 260 A), pattern I (intermediate-sized LDLs, LDL size > 255 A, < 260 A), and pattern B (small, dense LDLs, LDL size < or = 255 A). The LDL size decreased significantly in patients with the highest tertile of areas under the incremental curves (AUICs) of triglycerides above the fasting levels. The LDL phenotype shifted toward the smaller phenotype after a fat load in three of eight patients with pattern A and in seven of 35 patients with pattern I. The AUICs of triglyceride-rich lipoproteins were significantly higher in these patients than in the patients exhibiting little change in LDL size, whereas the fasting metabolic parameters were similar among the patients of the same LDL phenotype in the fasting state. These results suggest that alimentary lipaemia plays an important role in the remodeling of LDL particles into the more atherogenic small, dense LDLs in patients with MI.

W12.289 PPARγ activation lowers postprandial but not fasting triglyceride concentrations in type 2 diabetes: An investigation of tissue-specific mechanisms in humans

The present study was conducted to determine whether alimentary lipemia alters platelet activity in vivo. Normolipidemic volunteers were given a fatty meal and platelet function was assessed before, and 3 and 6 h after the meal. Platelet aggregability and secretion was determined using whole blood flow cytometry (expression of platelet P-selectin and fibrinogen binding), filtragometry ex vivo (reflecting platelet aggregability in vivo) and by measurements of platelet specific products in plasma (β-thromboglobulin and platelet factor 4). Plasma triglycerides increased from 0.8 (0.6:1.1; median, 25th and 75th percentiles) to 1.7 (1.0:2.3) mmol/l at 3 h and returned to baseline after 6 h (P<0.001, one-way ANOVA). Apo B-100 and apo B-48 were both markedly increased 3 h postprandially in the Sf 60–400 fraction (large VLDLs, P<0.001 for both), whereas the Sf 20–60 (small VLDLs) and Sf 12–20 fractions (IDL) did not change. The platelet function assessments revealed that the percentage of platelets expressing P-selectin increased by 40% (5%; 64%) after 3 h and by 51% (−7%; 85%) 6 h postprandially in unstimulated samples (P<0.05 for both). In samples stimulated by ADP in vitro P-selectin expression increased by 45% (6%; 58%) after 3 h and by 30% (12%; 58%) (P<0.01 for both) after 6 h at 0.1 μM. Platelet P-selectin expression was less influenced at higher ADP concentrations. The plasma levels of β-thromboglobulin (≈20 ng/ml) and platelet factor 4 (≈0.3 ng/ml) were not affected by the fat load. Flow cytometric analyses of fibrinogen binding and filtragometry measurements also failed to reveal any postprandial alterations. The present finding of enhanced platelet P-selectin expression suggests that platelets are mildly sensitized postprandially. Whether this is of importance for thrombus formation and atherosclerosis needs to be studied further.

Plasma tumour necrosis factor-α and early carotid atherosclerosis in healthy middle-aged men

Tumour necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine, which is implicated in some metabolic disorders and may play a role in the development of cardiovascular disease. We examined whether plasma TNF-alpha is related to established cardiovascular risk indicators, plasma levels of soluble cellular adhesion molecules and carotid artery intima-media thickness determined by ultrasound examination in a population-based cohort of 96 healthy 50-year-old men. TNF-alpha and cellular adhesion molecules were measured with enzyme-linked immunosorbent assays. Plasma TNF-alpha concentration was associated with systolic and diastolic blood pressure, degrees of alimentary lipaemia, plasma very low density lipoprotein triglyceride, low density lipoprotein (LDL) cholesterol concentrations and peak LDL particle size. Two indices of insulin resistance as well as all soluble cellular adhesion molecules correlated positively with TNF-alpha. The plasma TNF-alpha concentration was associated with common carotid intima-media thickness in univariate analysis. In contrast, soluble E-selectin and postprandial triglycerides, but not TNF-alpha, were independent determinants of common carotid intima--media thickness. The plasma TNF-alpha concentration is associated with degrees of early atherosclerosis and correlates with metabolic and cellular perturbations that are considered important for the vascular process.

Atherogenesis: Historical Perspective, Biochemical Mechanism, and Current Status

Collation and integration of diverse multidisciplinary research reports into a compatible sequence of biochemical reactions in atherosclerosis defines a primary dysfunctional site residing in the metabolic processing of acetyl Co-A in oxidative phosphorylation. This site, subject to dysfunctional gene expression in the later phase of the mammalian life process, is also subject to evolutionary genetic speciation events defined by orthologous genes. Depressed processing of acetyl Co-A in the citric acid-oxidative phosphorylation cycle can account for increased plasma free fatty acid (FFA), depressed clearing of alimentary lipemia, chylomicrons, increased uploading of plasma protein with lipid (LDL), increased plasma triglycerides and cholesterol, all of which serve as historical biochemical indices of atherosclerosis. Depressed function of this citric acid-oxidative phosphorylation sequence of biochemical reactions embraces multiple sequentially related reaction sites including deficient biosynthesis and transfer of methyl groups, deficient heparin induced lipoprotein lipase, declining rate of albumin biosynthesis, declining generation of high energy phosphate (ATP), increased generation or mobilization of FFA, increased thrombin, depressed activation of plasminogen and increased biosynthesis and turnover of fibrinogen into polymerized fibrin atheroma.

Insulin and non-esterified fatty acid relations to alimentary lipaemia and plasma concentrations of postprandial triglyceride-rich lipoproteins in healthy middle-aged men.

Enhanced and prolonged postprandial lipaemia is related to cardiovascular disease but how postprandial lipaemia is regulated is poorly known. We therefore determined the relations of fasting insulin concentrations to fasting and postprandial lipids, lipoproteins and non-esterified fatty acids in middle-aged men. The subjects, 99 healthy 50-year-old men with an apolipoprotein E3/3 genotype, ate a mixed meal. The apolipoprotein B-48 and B-100 contents were determined in triglyceride-rich lipoproteins as a measure of chylomicron remnant and very low density lipoprotein particle concentrations. Fasting plasma insulin was associated with the triglyceride response to the test meal, independently of body mass index, waist-to-hip circumference ratio, blood glucose and the insulin effect on fasting plasma triglycerides. Exaggerated and prolonged postprandial lipaemia in subjects in the upper quartile of the plasma insulin distribution was largely accounted for by large (Svedberg flotation rate > 60) very low density lipoproteins and chylomicron remnants. Insulin relations to large postprandial triglyceride-rich lipoproteins exclusively reflected the association between plasma insulin and the fasting plasma concentrations of these lipoprotein species, whereas plasma insulin and late postprandial plasma concentrations of small (Svedberg flotation rate 20-60) chylomicron remnants were related, independently of insulin influences on fasting concentrations. Strong positive relations were found between the late increases in large triglyceride-rich lipoproteins and plasma non-esterified fatty acid concentrations after 6 h. The degree of insulin sensitivity is a major determinant of postprandial lipaemia in healthy middle-aged men and could add to the regulation of the basal production of large triglyceride-rich lipoproteins.

Evidence for a cholesteryl ester donor activity of LDL particles during alimentary lipemia in normolipidemic subjects

Postprandial hypertriglyceridemia represents an independent risk factor for coronary artery disease. In the postprandial state, elevated levels of triglyceride-rich lipoproteins (TRL) are minor acceptors of HDL-cholesteryl ester (CE) transferred by CETP in normolipidemic subjects: indeed, LDL particles represent the major CE acceptors. In order to evaluate further the potential atherogenicity of lipoprotein particles characteristic of the postprandial phase in normolipidemic subjects, we determined the quantitative and qualitative features of apoB- and apoAI-containing lipoproteins over an 8-h period following consumption of a mixed meal. During postprandial lipemia, we observed a significant decrease (−12%) in plasma AI concentration (138±4 and 156±4 mg/dl, at 3 h and baseline, respectively, P<0.005). Concomitantly, a progressive increase (+13%) was detected in HDL2 concentrations (138±7 mg/dl at 4 h vs. 122±12 mg/dl at baseline, P<0.005), as well as a significant reduction (−9%) in HDL3 levels (137±6 mg/dl at 3 h vs. 150±4 mg/dl at baseline; P<0.05). Additionally, plasma LDL was reduced by 5% (247±12 mg/dl at 3 h vs. 260±15 mg/dl at baseline; P<0.05) 3 h following meal intake. Moreover, a significant reduction (−10%) occurred in the CE/TG ratio in LDL at 2 h postprandially (8±2 at 2 h vs. 9±3 at baseline; P<0.005). These changes reflected an increment (17±3 mg/dl at 3 h vs. 15±4 mg/dl at baseline; P<0.05) in LDL triglyceride concentrations. Despite the high CE acceptor capacity of LDL particles, no measurable increase in their CE content was detected during the postprandial phase. We demonstrated that CE accepted by LDL particles from HDL are secondarily transferred to chylomicrons by CETP. As chylomicrons displayed a 260-fold lower CE/TG ratio than LDL (0.03:1 and 7.8:1 in chylomicrons and LDL, respectively), CE-rich LDL may act to donate CE to chylomicrons. In conclusion, our data indicate that the presence of elevated levels of chylomicrons induces LDL to act as a secondary donor of CE during the postprandial phase.

Alimentary lipemia, postprandial triglyceride-rich lipoproteins, and common carotid intima-media thickness in healthy, middle-aged men.

Alimentary lipemia has been associated with coronary heart disease and common carotid artery intima-media thickness (IMT). This study was designed to investigate the relations of subclasses of postprandial triglyceride-rich lipoproteins (TRLs) with IMT. Ninety-six healthy 50-year-old men with an apolipoprotein (apo) E3/E3 genotype underwent an oral fat tolerance test and B-mode carotid ultrasound examination. The apo B-48 and apo B-100 contents of each fraction of TRLs were determined as a measure of chylomicron remnant and VLDL particle concentrations. In the fasting state, LDL cholesterol (P<0.05) and basal proinsulin (P<0. 05) were significantly related to IMT, whereas HDL cholesterol, plasma triglycerides, and insulin were not. In the postprandial state, plasma triglycerides at 1 to 4 hours (P<0.01 at 2 hours), total triglyceride area under the curve (AUC) (P<0.05), incremental triglyceride AUC (P<0.01), and the large VLDL (Sf 60 to 400 apo B-100) concentration at 3 hours (P<0.05) were significantly related to IMT. Multivariate analyses showed that plasma triglycerides at 2 hours, LDL cholesterol, and basal proinsulin were consistently and independently related to IMT when cumulative tobacco consumption, alcohol intake, waist-to-hip circumference ratio, and systolic blood pressure were included as confounders. These results provide further evidence for postprandial triglyceridemia as an independent risk factor for early atherosclerosis and also suggest that the postprandial triglyceridemia is a better predictor of IMT than particle concentrations of individual TRLs.

Magnitude of alimentary lipemia is related to intima-media thickness of the common carotid artery in middle-aged men

Fat intake leads to generation of potentially atherogenic triglyceride-rich lipoproteins (TRL). To investigate the relationship between early atherosclerotic changes and accumulation of hepatic and intestinal TRL after oral fat intake, an estimate of the intima-media thickness (IMT) was made using ultrasound of the common carotid artery, and postprandial TRL was quantified during a standardized oral fat tolerance test in 30 healthy normo- and hypertriglyceridemic middle-aged men. At base line the expected positive association between the LDL cholesterol level and the IMT of the common carotid artery was observed ( r=0.53, P<0.01). In addition, postprandial plasma triglycerides, in particular those measured late (6 h) after intake of the test meal, correlated positively with the IMT ( r=0.44, P<0.05). Of note, this latter correlation was independent of both the LDL cholesterol and the fasting plasma triglyceride concentrations. In a multivariate analysis, 39% of the total variability for the common carotid IMT were explained by age, LDL cholesterol and the postprandial triglyceride level. In univariate analysis, few statistically significant relations were found between common carotid IMT and postprandial levels of chylomicron remnants, VLDL and VLDL remnants of different particle size, the latter determined by specific measurements of ApoB-48 and ApoB-100 in subfractions of TRL. Therefore, in healthy middle-aged men, elevated postprandial triglyceride levels might identify a metabolic state related to early atherosclerosis.

Alimentary Lipemia Is Enhanced in Fiber-Fed Rats

The effect of dietary fiber on the pattern of postprandial lipemia was examined in two studies with male Wistar rats. In the first study, groups of rats were killed after food deprivation (0 h) or 1, 4.5 or 8.5 h after a high fat test meal containing either cellulose (CL) or oat bran (OB). Plasma triglycerides (TG) were higher in the OB group at 4.5 h compared with both the 0-h and the CL-groups at 4.5 h. In both groups, LDL and TG-rich lipoprotein cholesterol (TRL-C) concentrations were higher at 8.5 h than at 0 h; HDL cholesterol was significantly lower at 8.5 h than at 0 h for the OB group only. The enhanced lipemia when OB was fed may stimulate cholesterol movement from HDL to LDL and TRL. To examine whether TRL secretion rates were responsible for the enhanced lipemia, a second study was conducted. Rats were fitted with jugular catheters and allowed to recover. Two groups were fed either CL or OB and infused with Triton-1339 (400 mg/kg). Two control groups were not fed and were infused with either Triton or saline. Rats were killed 2.5 h after infusion. Plasma TG was 10-fold higher in the Triton group than in the saline group, but did not differ between the OB and CL groups. The relative contribution of TRL-C to total cholesterol was significantly greater in the Triton control than in the OB and CL groups. Enhanced secretion of TRL was not responsible for the lipemia observed in the first study. Rather, alterations in clearance rate were responsible.