Remnant-like Particle Triglyceride Research Articles

Post-prandial Remnant Lipoprotein Metabolism in Sitosterolemia

Aim: We aimed to clarify post-prandial accumulation of remnant-like particles (RLP) in patients with sitosterolemia.Methods: Oral fat tolerance test cream (Jomo Shokuhin, Takasaki, Japan) 50 g was given per body surface area (m2); blood sampling was performed at 2 h intervals up to 6 h. Plasma lipoprotein fractions and RLP fractions were determined in four sitosterolemic subjects with double mutations in ATP-binding cassette (ABC) sub-family G member 5 or member 8 (ABCG5 or ABCG8) gene (mean age = 18 yr, median low-density lipoprotein cholesterol [LDL-C] = 154 mg/dL), six heterozygous carriers (mean age = 31 yr, median LDL-C = 105 mg/dL), and five subjects with heterozygous familial hypercholesterolemia (FH, mean age = 32 yr, median LDL-C = 221 mg/dL). The incremental area under curve (iAUC) of lipids, including LDL-C, apolipoprotein B-48 (apoB48), RLP cholesterol (RLP-C), and RLP triglyceride (RLP-TG) were evaluated.Results: After oral fat load, there was no significant difference of the iAUC of LDL-C between sitosterolemia and heterozygous FH, whereas the iAUC of apoB48 was significantly larger in the sitosterolemic subjects compared with that of heterozygous FH (2.9 µg/mL × h vs. 1.3 µg/mL × h, p < 0.05). Under these conditions, the iAUCs of RLP-C and RLP-TG levels were significantly larger in the sitosterolemic subject compared with those of heterozygous FH (9.5 mg/dL × h vs. 5.7 mg/dL × h, p < 0.05; 149 mg/dL × h vs. 40 mg/dL × h, p < 0.05, respectively), whereas those of heterozygous carriers were comparable with those with heterozygous FH.Conclusions: Post-prandial lipoprotein metabolism in sitosterolemia appeared to be impaired, leading to their elevation in serum sterol levels. (UMIN Clinical Trials Registry number, UMIN000020330)

Effects of taurine intake on serum lipids in young women

Background: Taurine is an abundant amino acid in human cells, promoting ocular and biliary health, which is also used to treat congestive heart failure, hypertension, and hepatitis. Recently, taurine-enriched energy drinks have become popular with young adults, but the effects of taurine on serum lipids in young adults are unknown.Objective: We studied the influence of oral administration of taurine on serum lipid levels in healthy young women.Methods: Ten healthy young women with a mean body mass index of 20.0kg/m2, apolipoprotein E (apoE) phenotype 3/3 and normal menstrual cycles participated. Each subject was instructed to orally ingest 1g of taurine powder after each meal (3g/day) in addition to their usual diets during one menstrual cycle. Before and at the end of taurine intake, physical measurements and blood collection were performed in the morning after a 12-h fast, and 3-day weighted dietary records were obtained. Concentrations of serum lipids, apolipoproteins, and fatty acids in the serum phospholipid fraction were measured.Results: The subjects showed good compliance with taurine intake and none reported adverse effects during the experimental period. After taurine intake, concentrations of total cholesterol, low density lipoprotein cholesterol (LDL-C), free cholesterol, and apolipoprotein B (apoB) increased (p&lt;0.05), while phospholipids tended to increase (p=0.051). Fatty acids in the serum phospholipid fraction also significantly increased (p&lt;0.05). However, triglyceride, remnant-like particle cholesterol, remnant-like particle triglyceride, apoE, the apolipoprotein A-1 (apoA- 1)/apoB ratio and the LDL-C/apoB ratio were unchanged. Furthermore, body weight was significantly increased (p&lt;0.01), but did not correlate with changes either in serum lipids or nutrient intakes.Conclusion: These results suggest that high taurine intake affects lipoprotein metabolism and increases serum lipids in slightly lean young women.Key Words: Taurine, slightly lean young women, serum lipids, remnant lipoprotein, fatty acids of the serum phospholipid fraction.

Impact of Serum Retinol-Binding Protein 4 Levels on Regulation of Remnant-Like Particles Triglyceride in Type 2 Diabetes Mellitus

Background. Although retinol-binding protein 4 (RBP4) associates with insulin resistance and remnant-like particles triglyceride (RLP-TG) elevated in the insulin resistant state, few data exist regarding the relationship between RBP4 and RLP-TG. Subjects and Methods. The study included 92 Japanese type 2 diabetic mellitus (T2DM) male patients (age 60.5 ± 13.6 years, body mass index (BMI) 24.7 ± 4.1 kg/m2, waist circumference (WC) 88.4 ± 10.7 cm, and HbA1c (NGSP) 7.2 ± 1.9%). Patients on medications affecting insulin sensitivity, including fibrates, biguanides, and thiazolidinedione, were excluded. Visceral fat area (VFA) and subcutaneous fat area (SFA) were measured by computed tomography. Results. RBP4 levels showed a significant positive correlation with RLP-TG (r = 0.2544 and P = 0.0056), TG (r = 0.1852 and P = 0.041), RLP-TG/TG (r = 0.23765 and P = 0.0241), and age (r = −0.2082 and P = 0.0219), although there was no significant correlation with VFA, SFA, adiponectin levels, or homeostasis model of assessment insulin resistance (HOMA-R). Multiple regression analysis revealed that RBP4 was an independent determinant of RLP-TG (P = 0.0193) but was not a determinant of TG. Conclusions. RBP4 correlates positively with serum RLP-TG independent of fat accumulation in T2DM. RBP4 may regulate remnant metabolism independent of glycemic control in T2DM.

Eicosapentaenoic Acid Supplementation Changes Fatty Acid Composition and Corrects Endothelial Dysfunction in Hyperlipidemic Patients

We investigated the effects of purified eicosapentaenoic acid (EPA) on vascular endothelial function and free fatty acid composition in Japanese hyperlipidemic subjects. In subjects with hyperlipidemia (total cholesterol ≥220 mg/dL and/or triglycerides ≥150 mg/dL), lipid profile and forearm blood flow (FBF) during reactive hyperemia were determined before and 3 months after supplementation with 1800 mg/day EPA. Peak FBF during reactive hyperemia was lower in the hyperlipidemic group than the normolipidemic group. EPA supplementation did not change serum levels of total, HDL, or LDL cholesterol, apolipoproteins, remnant-like particle (RLP) cholesterol, RLP triglycerides, or malondialdehyde-modified LDL cholesterol. EPA supplementation did not change total free fatty acid levels in serum, but changed the fatty acid composition, with increased EPA and decreased linoleic acid, γ-linolenic acid, and dihomo-γ-linolenic acid. EPA supplementation recovered peak FBF after 3 months. Peak FBF recovery was correlated positively with EPA and EPA/arachidonic acid levels and correlated inversely with dihomo-γ-linolenic acid. EPA supplementation restores endothelium-dependent vasodilatation in hyperlipidemic patients despite having no effect on serum cholesterol and triglyceride patterns. These results suggest that EPA supplementation may improve vascular function at least partly via changes in fatty acid composition.

Miglitol suppresses the postprandial increase in interleukin 6 and enhances active glucagon-like peptide 1 secretion in viscerally obese subjects

Visceral obesity and insulin resistance are regarded as risk factors for atherosclerosis. Epidemiologic studies have demonstrated long-term anti-atherosclerotic effects with administration of α-glucosidase inhibitors. α-Glucosidase inhibitors also have been reported to enhance glucagon-like peptide 1 (GLP-1) secretion. We compared the postprandial effects of a single administration of miglitol and acarbose on glucose and lipid metabolism, on insulin requirement, on GLP-1 secretion, and on inflammatory and endothelial markers in viscerally obese subjects. Twenty-four viscerally obese subjects with relative insulin resistance participated in this study. Subjects were given a single dose of miglitol (50 mg), acarbose (100 mg), or placebo blindly and randomly before a meal in a crossover design. The meal loads after drug administration were tested 3 times within 2 weeks. We measured glucose, insulin, lipids, lipoprotein lipase, interleukin 6, intracellular adhesion molecule 1, vascular cell adhesion molecule 1, and active GLP-1 at before and various minutes after the meal. Single administration of both α-glucosidase inhibitors had several beneficial effects in improving postprandial hyperglycemia and reducing postprandial insulin requirement approximately 25% of placebo without adversely affecting lipid profiles. Although lipoprotein lipase levels within 2 hours after the meal did not show differences among miglitol, acarbose, and placebo administrations, miglitol significantly suppressed the increases in triglycerides, remnant-like particle triglycerides, and remnant-like particle cholesterol compared to acarbose and placebo in the early phase. Miglitol also significantly enhanced active GLP-1 secretion to a greater extent than acarbose ( P < .01) and placebo ( P < .001), and significantly suppressed the postprandial increase in interleukin 6 compared to placebo ( P < .01). The results point to the potential suitability of miglitol as an anti-atherosclerotic effect in viscerally obese subjects, in preference to acarbose. Further studies are needed to elucidate the long-term effects on enhanced GLP-1 secretion and anti-atherosclerosis.

The Relationship of Serum Lipoprotein Lipase Mass with Fasting Serum Apolipoprotein B-48 and Remnant-like Particle Triglycerides in Type 2 Diabetic Patients

There have been no previous reports showing specifically the relation between lipoprotein lipase (LPL) and apolipoprotein (apo) B-48 or remnant metabolism. In this study, we have clarified the relationships of LPL mass in pre-heparin with serum apo B-48 measured by enzyme-linked immunosorbent assay, triglycerides (TG), and remnant-like particle triglycerides (RLP-TG). Seventy-nine type 2 diabetic subjects [age, 55+/-13; body mass index (BMI), 25+/-5.0 kg/m2; fasting plasma glucose (FPG), 7.39+/-2.22 mmol/l, HbA1c, 6.5+/-1.3%, total cholesterol (TC), 5.36+/-1.09 mmol/l, TG, 2.32+/-2.53 mmol/l; HDL-C, 1.22+/-0.44 mmol/l; serum LPL mass, 45+/-22 ng/ml; apo B-48, 6.6+/-6.3 microg/ml] were recruited in this study. Fasting serum apo B-48 were measured by ELISA using anti-human apo B-48 monoclonal antibodies (MoAb) and LPL mass by ELISA using anti-bovine milk LPL MoAb. RLP-TG levels were measured using monoclonal antibodies to apo B-100 and apo A-1. There was no relationship of LPL mass to age, BMI, FPG, and HbA1c. Serum LPL mass was correlated inversely with TG (r=-0.529 p<0.0001) and positively with HDL-C (r=0.576, p<0.0001). Also, LPL mass showed inverse correlations with apo B-48 (r=-0.383 p<0.0001) and RLP-TG (r=-0.422 p<0.0001, n=51). Multiple regression analysis with TG, apo B-48, or RLP-TG as dependent variables, and age, gender, BMI, plasma glucose, and LPL mass as independent variables showed that LPL mass was associated independently with TG, apo B-48, or RLP-TG. The decrease in LPL protein mass could cause an increase in serum apo B-48 and RLP-TG levels, which is related to the retardation of remnant metabolism.

Influence of Aging and Menopause on Postprandial Lipoprotein Responses in Healthy Adult Women

To analyze the influence of menopause and age on postprandial lipoprotein responses in healthy adult women. Twenty-seven healthy young and middle-aged pre- and postmenopausal female volunteers aged 21-53 y were enrolled. They ingested OFTT cream(Jomo, Takasaki, Japan). Fasting and postprandial blood samples were obtained for up to 6 h, and serum concentrations of lipoproteins were analyzed. In the postprandial phase, serum triglycerides(TG), remnant-like particle(RLP)-TG(RLP-TG), RLP-cholesterol(RLP-C), and TG-rich lipoprotein-TG(TRL-TG)concentrations in all groups peaked after 2 h. After 4 h, the TG, RLP-C, RLP-TG and TRL-TG concentrations in the young women returned to the fasting concentrations. However, at 6 h, these parameters in the pre- and postmenopausal women had barely returned to the fasting concentrations. The present results suggest that:(1)the magnitude of postprandial TG concentrations is dependent on age, but not on menopause;(2)clearance of remnant lipoproteins is delayed with age in pre- and postmenopausal women compared to young women, and(3)menopause is associated with an increase of RLP-C, but may not influence LDL particle size.

Analysis of the Factors Contributing to Serum Retinol Binding Protein and Transthyretin Levels in Japanese Adults

We examined various factors possibly related to metabolic syndrome, particularly focusing on nutritional assessment proteins such as retinol binding protein (RBP) and transthyretin (TTR), and remnant lipoproteins. Fasting serum lipid was analyzed in 58 Japanese adult volunteers (33 men and 25 women, 42.5 +/- 10.1 years old). The lipid profiles of the subjects were classified by lipoprotein polyacrylamide gel electrophoretic patterns into Types S (n = 10), A (n = 37), and N (n = 11), according to the method described in Internal Medicine 42: 244, 2003. RBP and TTR were significantly higher in Type N than in Types S and A. In multivariate analysis, RBP was accounted for by remnant-like particle-triglyceride (RLP-TG), interleukin 6, body mass index and low-density lipoprotein (LDL)-cholesterol (adjusted R2 = 0.621). TTR was accounted for by lipoprotein(a), adiponectin and RLP-TG (adjusted R2 = 0.415). Malondialdehyde-LDL was significantly accounted for by LDL-cholesterol and RLP-cholesterol (adjusted R2 = 0.601). Lipoprotein(a) and LDL-cholesterol were independent variables for oxidized LDL antigen (adjusted R2 = 0.620). High-sensitivity C-reactive protein was accounted for by interleukin 6, immunoreactive insulin and oxidized LDL antigen (adjusted R2 = 0.361). Uric acid and body mass index were independent variables for adiponectin (adjusted R2 = 0.429). RBP and TTR may be useful as convenient and simple clinical markers of overnutrition and possibly of metabolic syndrome.

Serum sphingomyelin levels are related to the clearance of postprandial remnant-like particles

It is known that sphingomyelin (SM) content is higher in apolipoprotein B-containing particles (BLps) than in high density lipoproteins and that BLp levels, including chylomicrons and their remnant particles, are positively related to atherosclerosis. To evaluate the relationship between serum SM and postprandial remnant particle levels, we determined SM, triglyceride (TG), and cholesterol levels in serum and in remnant-like particles (RLPs) before and 3, 5, 7, and 10 h after a high-fat meal in 31 healthy subjects. We found that serum SM, like serum TG, was increased to its maximum 3 h after fat loading and then gradually decreased to basal levels after 10 h. More important, we determined that SM and TG levels in RLPs were parallel. Serum SM was positively correlated with serum TG (P <0.001), RLP SM (P <0.001), RLP TG (P <0.001), and RLP cholesterol (P <0.001) levels. It is our conclusion that serum SM is a marker for the clearance of RLPs.

Association Between Postprandial Remnant-like Particle Triglyceride (RLP-TG) Levels and Carotid Intima-Media Thickness (IMT) in Japanese Patients with Type 2 Diabetes: Assessment by Meal Tolerance Tests (MTT)

Our study evaluated the relationship between the pathologic changes associated with atherosclerosis, as primarily represented by postprandial remnant-like lipoproteins and carotid intima-media thickness (IMT), in type 2 diabetic patients. Meal tolerance tests (MTT) were performed in 68 patients with type 2 diabetes. The subjects were divided by pre-meal and 2-h postprandial triglyceride (TG) levels into the normotriglyceridemia (NTG) group; the postprandial hypertriglyceridemia (PHTG) group; and the fasting hypertriglyceridemia (FHTG) group. HOMA-R values were significantly higher in the FHTG group than in the NTG group, with the plasma pre-heparin LPL mass and serum adiponectin levels in the FHTG and PHTG groups significantly lower than in the NTG group. One- and two hour postprandial RLP-TG levels were significantly higher in the PHTG group than in the NTG group, while there was no significant difference in postprandial glucose levels between the two groups. The IMT values were significantly higher in both the FHTG and PHTG groups than in the NTG group. Logistics regression analysis of the 1- and 2-h RLP-TG values using IMT as an induced variable showed the odds ratio for high IMT values to be 5.17 (p < 0.05) for the 1-h RLP-TG values and 3.01 (p = 0.105) for the 2-h RLP-TG values. Our study results suggest that delayed TG metabolism leading to the retention of remnants in type 2 diabetic patients appears to be closely associated with atherosclerosis, and that postprandial hyperlipidemia is an independent risk factor for the early onset of atherosclerosis.

Effect of remnant-like particle on shear-induced platelet activation and its inhibition by antiplatelet agents

Remnant-like particles (RLPs) have been reported to promote atherosclerosis and to have effects on platelet function. We studied the effects of RLP on shear-induced platelet activation and their inhibition by antiplatelet agents in vitro. RLP were separated using two monoclonal antibodies, anti apo B-100 and anti apo A-I. These RLP fractions were added to whole blood (WB) or platelet-rich plasma (PRP) in serial dilution of 1, 10 or 100 μg RLP triglyceride (TG) per ml of total sample volume. These samples were incubated, and then stimulated with a high shear stress of 108 dyn/cm 2. Shear-induced platelet aggregation (SIPA) was calculated from the percentage of single platelet loss. P-selectin expression on platelet surface and platelet-derived microparticle (PMP) generation were measured before and after stimulation with shear stress using flow cytometer. SIPA was significantly enhanced by RLP in WB but not in PRP. This enhancing effect was not dose-dependent and was greatest at 10 μg TG/ml. P-selectin expression induced by shear stress was only enhanced by RLP at a concentration of 100 μg TG/ml in both WB and PRP, while generation of PMP induced by shear stress was only enhanced by RLP at a concentration of 100 μg TG/ml in WB. Aspirin inhibited only the enhancement of SIPA by RLPs, while cilostazol inhibited the enhancement of not only SIPA but also p-selectin expression and PMP generation by RLPs.

Remnant-like lipoproteins, hormone therapy, and angiographic and clinical outcomes: The Women's Angiographic Vitamin & Estrogen trial

Background Little is known about the impact of post-menopausal hormone therapy on remnant-like particle (RLP) concentrations and about the relationship between RLP concentration and angiographic progression of coronary artery disease and clinical events in women. Methods RLP cholesterol and triglyceride levels were measured at baseline and 3 months after randomization in 397 post-menopausal women enrolled in The Women's Angiographic Vitamin & Estrogen (WAVE) trial. Correlates of baseline RLP levels and changes in levels with post-menopausal hormone therapy were determined with multiple linear regression. Coronary angiography was performed at baseline and after a mean of 2.9 years. Changes in minimal and average luminal diameter were modeled with multivariate linear regression, clinical outcomes (non-fatal myocardial infarction, stroke, or cardiovascular death) with multiple logistic regression. Results The mean subject age was 65 years, 66% of subjects were white, 18% of subjects smoked, most subjects were overweight or obese, and 35% of subjects had diabetes mellitus. RLP cholesterol (0.277 ± 0.254 mmol/L) and triglyceride (0.386 ± 0.552 mmol/L) levels corresponded approximately to the 90th percentile in women in the Framingham study. RLP levels did not change significantly with hormone therapy. RLP levels at baseline, changes in RLP levels, and on treatment RLP levels did not relate to angiographic changes or clinical outcomes (non-fatal myocardial infarction, stroke, or cardiovascular death). Conclusions RLP levels were high among post-menopausal women enrolled in the WAVE study, were not affected by hormone therapy, and did not relate to angiographic progression of coronary artery disease or clinical outcomes.

Effects of Nateglinide on the Elevation of Postprandial Remnant-like Particle Triglyceride Levels in Japanese Patients with Type 2 Diabetes Assessment by Meal Tolerance Test

To elucidate the role of early insulin response in post-prandial hyperlipidemia, we examined triglyceride (TG) and remnant-like particle triglyceride (RLP-TG) levels, using a meal tolerance test (MTT) with or without the administration of nateglinide (NAT). The MTTs were performed 2 d apart in 36 drug-naive patients with type 2 diabetes who had been hospitalized for glycemic control while receiving diet therapy. Before the second MTT, patients were treated with 90 mg NAT. Treatment with NAT was associated with a significant increase in insulin levels in the treated patients 1 h after the test meal, compared to levels in non-treatment. NAT treatment was also associated with a significant decrease in the level of free fatty acids 1 and 2 h after the meal, and with a significant decrease in plasma glucose levels 1, 2, and 4 h after the meal, compared to those in non-treatment. During the first MTT with NAT non-treatment, 13 patients showed serum TG levels of 200 mg/dL or greater when measured 2 h after the meal. In these 13 patients, NAT administration produced a significant decrease in TG levels 1, 2, and 6 h after the meal, as well as a significant reduction in RLP-TG levels 1 and 2 h after the meal. NAT administration was also associated with significant reductions in area under the curve (DeltaAUC) for TG and RLP-TG. These results suggest that, in a clinical setting, the early insulin response is closely associated with both postprandial glucose and postprandial lipid metabolism in Japanese patients with type 2 diabetes.

Serum concentrations of remnant-like particles in hypothyroid patients before and after thyroxine replacement.

Remnant-like particles (RLPs) reflect chylomicron remnants and very-low-density lipoprotein remnants, which are most likely to be atherogenic particles. To investigate the effect of thyroxine replacement on the metabolism of RLPs in hypothyroidism, we measured serum concentrations of RLPs during an oral fat-loading test in patients with hypothyroidism before and after thyroxine replacement. Thirteen patients with hypothyroidism, having serum-free thyroxine (FT4) of 4.25 +/- 2.23 pmol/l (mean +/- SD) and TSH of 72.5 +/- 27.7 mU/l, participated in the study. Two-hundred grams of cream containing 32.9% of fat were given to each patient followed by blood draws every 2 h for 8 h. The patients became euthyroid after 3 months of T4 replacement, and the fat-loading tests were then repeated. Fasting levels of serum total cholesterol and low-density lipoprotein cholesterol were remarkably decreased after T4 therapy (P < 0.0005). Serum high-density lipoprotein cholesterol and triglyceride were also decreased by T4 therapy, not so remarkably but significantly (P < 0.05). Activities of lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) increased 52% and 85%, respectively, from the pretreatment values. Serum concentrations of remnant-like particle cholesterol (RLP-C) and remnant-like particle triglyceride (RLP-TG), measured by immunoseparation assays, significantly decreased from 0.14 +/- 0.03 to 0.09 +/- 0.03 mmol/l (P < 0.0005) and from 0.19 +/- 0.11-0.11 +/- 0.07 mmol/l (P < 0.01), respectively. In the fat-loading test, serum low-density lipoprotein cholesterol concentrations were not changed, while serum RLPs concentrations were increased and remained high throughout the test, with the peak value at 6 h in a hypothyroid condition. In an euthyroid condition after T4 therapy, the peak values of RLPs were obtained at 4 h, and the concentrations were decreased rapidly. As the result, areas under the curve of serum RLPs were decreased remarkably after T4 therapy. Hypothyroidism seems to be associated with a decrease in metabolism of serum RLPs. Such altered metabolism of RLPs may be related to the decreased activities of LPL and HTGL and can be corrected by T4 replacement therapy.

Estrogen treatment of prostate cancer increases triglycerides in lipoproteins as demonstrated by HPLC and immunoseparation techniques

Background: Estrogen administration is known to increase serum triglyceride concentrations. This study measured changes in lipoproteins of patients with prostate cancer treated with estrogen to determine whether the increased triglyceride concentrations are associated with atherogenic lipoprotein patterns. Methods: Fifteen patients (52–87 years) with histologically diagnosed prostate cancer received diethylstilbestrol diphosphate (250 mg/day). Serum samples were collected before and after 1 and 2 weeks of treatment. Cholesterol and triglyceride profiles of major lipoproteins were determined by HPLC, remnant-like particle cholesterol and triglyceride concentrations by an immunoseparation technique, and apolipoproteins by immunologic methods. Results: Estrogen treatment induced a 63.3% increase in total triglyceride concentrations, which occurred in all major lipoprotein classes with significant increases in HDL-triglycerides (130.4%), LDL-triglycerides (60.7%) and VLDL-triglycerides (56.2%). HDL-cholesterol increased significantly by 26.8%, while LDL-cholesterol decreased (15.6%). Remnant-like particle triglyceride concentrations also increased significantly by 77%, whereas remnant-like particle cholesterol concentrations remained unchanged. Apolipoproteins A-I and A-II increased; apolipoprotein E and Lp(a) decreased. Conclusions: The techniques used here conveniently demonstrated that short-term estrogen treatment in prostate cancer patients resulted in triglyceride enrichment of all major lipoprotein classes but did not induce changes in the lipoprotein profiles generally recognized as increasing risk for cardiovascular disease, except for the elevation of plasma triglyceride and remnant-like particle triglyceride.

Comparison of fasting and postprandial plasma lipoproteins in subjects with and without coronary heart disease

Plasma lipoprotein levels, including remnant-like particle (RLP) cholesterol and RLP triglycerides, were assessed in fasting (12 hours) and postprandial (PP) (4 hours after a fat-rich meal) states in 88 patients with coronary heart disease (CHD) and 88 controls. All lipoproteins were assessed by direct methods. We hypothesized that patients with CHD would have greater percent increases in their triglyceride levels, RLP cholesterol, and RLP triglycerides, in response to a fat-rich meal. In the fasting state, triglycerides, RLP cholesterol, RLP triglycerides, and low-density lipoprotein (LDL) cholesterol levels were all significantly higher in cases versus controls by 51%, 35%, 39%, and 40%, respectively. These levels were 57%, 37%, 64%, and 37% higher in the PP state, respectively. Mean high-density lipoprotein (HDL) cholesterol values were 27% lower in cases in both the fasting and PP states. After eating, triglycerides, RLP cholesterol, and RLP triglycerides increased 64%, 71%, and 290% in controls, respectively, whereas in cases these levels increased by 71%, 94%, and 340%, respectively (all p <0.0001). Percent increases in the PP state were not significantly different in cases versus controls. Following the fat-rich meal, LDL and HDL cholesterol decreased by 5% and 4% in controls, and by 7% and 6% in patients, with no significant difference in percent changes between groups. Fasting values correlated very highly with PP values for all parameters (all p <0.0001). Our data indicate that although patients with CHD have higher fasting and PP levels of triglycerides, RLP cholesterol, and RLP triglycerides than controls, the response (percent increase) to a fat-rich meal is comparable in both groups. Thus, a feeding challenge is not essential for assessment of these lipoproteins. Moreover, it is not necessary to obtain a fasting sample to assess direct LDL and HDL cholesterol.

Remnant-like particle cholesterol, triglycerides, and insulin resistance in nonobese Japanese type 2 diabetic patients.

The aim of the study was to investigate the relationships between remnant-like particle (RLP) cholesterol, triglycerides, and insulin resistance in nonobese Japanese type 2 diabetic patients. A total of 86 nonobese Japanese type 2 diabetic patients (72 men and 14 women, aged 40-83 years, BMI 20.1-26.6 kg/m2) were studied. BMI, HbA1c levels, and fasting concentrations of plasma glucose, serum lipids (RLP cholesterol, total cholesterol, HDL cholesterol, and triglycerides), and serum insulin were measured. Insulin resistance was estimated by the homeostasis model assessment (HOMA-IR). The subjects were divided into two groups according to the value of HOMA-IR. Values >2.5 were indicative of the insulin-resistant state, and values <2.5 were indicative of the insulin-sensitive state. The insulin-resistant group had significantly higher RLP cholesterol and triglyceride levels and lower HDL cholesterol levels compared with the insulin-sensitive group. Univariate regression analysis showed that insulin resistance was positively correlated with BMI (r = 0.254, P = 0.019), HbA1c levels (r = 0.278, P = 0.011), RLP cholesterol levels (r = 0.315, P = 0.004), and triglyceride levels (r = 0.332, P = 0.002) and was negatively correlated with HDL cholesterol levels (r = -0.301, P = 0.006) in our diabetic patients. Multiple regression analysis showed that insulin resistance was independently associated with serum triglyceride levels, which explained 13.5% of the variability of insulin resistance in our nonobese Japanese type 2 diabetic patients. These results indicate that 1) nonobese Japanese type 2 diabetic patients with insulin resistance are characterized by high RLP cholesterol and triglyceride levels, and low HDL cholesterol levels; and 2) the level of serum triglycerides is an independent predictor of insulin resistance in these patients.

Plasma Level of Triglyceride-rich Lipoprotein Remnants Is Closely Associated with the Activation of Coagulation Factor VII in Patients with Myocardial Infarction

Remnant-like particles, which have been recognized to be atherogenic derivatives of chylomicrons and very low density lipoproteins, can be measured using a new assay kit. The purpose of the present study was to investigate the association of remnant-like particles with the coagulation system that has an important role in the pathogenesis of myocardial infarction. We assayed blood levels of total cholesterol, triglyceride, HDL-cholesterol, apolipoproteins, remnant-like particles-cholesterol, remnant-like particles-triglyceride, fibrinogen, factor VII antigen, activated factor VII, and tissue factor in 111 patients with a history of myocardial infarction and 128 control subjects. In simple regression analysis, plasma levels of remnant-like particles-cholesterol and remnant-like particles-triglyceride showed a significant positive correlation with the levels of activated factor VII ( r=0.319, p<0.001, and r=0.286, p=0.002, respectively) and the activated factor VII/factor VII antigen ratio ( r=0.241, p=0.011, and r=0.249, p=0.008, respectively) in patients with myocardial infarction. In contrast, there were no significant differences between remnant-like particles and activated factor VII in control subjects. In stepwise multivariate regression analysis, the significant determinants of activated factor VII were remnant-like particles-cholesterol (10.2%), apolipoproteins A-I (5.1%), and E (7.1%); for the activated factor VII/factor VII antigen ratio, remnant-like particles-triglyceride (6.2%), age at blood sampling (5.1%), and apolipoprotein A-I (4.0%) in patients with myocardial infarction. However, the significant determinants of activated factor VII and the activated factor VII/factor VII antigen ratio were HDL-cholesterol (9.9% and 9.2%, respectively) in control subjects. It is concluded that remnant-like particles may be a risk factor for myocardial infarction by activating the extrinsic coagulation pathway.

Remnant-like particle cholesterol and triglyceride levels of hypertriglyceridemic patients in the fed and fasted state

Potentially atherogenic triglyceride-rich lipoprotein (TRL) remnants can be isolated and quantitated as remnant-like particles (RLP), using an immunoaffinity gel containing specific anti-human apolipoprotein A-I (apoA-I) and apoB-100 monoclonal antibodies. The aim of the present study was to determine the relationship between postprandial changes in RLP levels and changes in total serum triglyceride (TG) in patients with different forms of hypertriglyceridemia (HTG). Three groups of patients were selected, having similarly elevated serum TG levels: a) HTG with TRL remnant accumulation (i.e., type III patients, n = 15, TG: 3.8 +/- 0.2 mm), b) HTG with increased LDL (i.e., type IIb patients, n = 15, TG: 3.7 +/- 0.2 mm), and c) HTG without evidence of remnant or LDL accumulation (i.e., type IV patients, n = 15, TG: 3.9 +/- 0.3 mm). Ingestion of a 45-g fat meal caused a significant increase in serum TG (30;-50%) in all patients. Mean serum TG levels of the three groups were not significantly different at 4 or 6 h after the meal. RLP cholesterol (C) and TG levels increased after the meal in all patients, but these postprandial increases were also not significantly different among groups. Type III patients had significantly higher (P < 0.01) levels of RLP-C and RLP-apoE in the fasted and fed state, and also had significantly higher RLP-C-to-serum TG ratios (P < 0.001) compared with the other groups. These results indicate that 1) RLP-C and RLP-TG levels are significantly increased in the fed versus fasted state in patients with elevated fasting TG levels; 2) patients with different forms of HTG, but similar TG levels, have similar postprandial increases in RLP-C and RLP-TG; and 3) type III patients have significantly elevated levels of RLP-C and RLP-apoE in both the fed and fasted state.

Plasma levels of remnant particles are determined in part by variation in the APOC3 gene insulin response element and the APOCI–APOE cluster

Remnant particles of triglyceride-rich lipoproteins (RLP) are known to be a strong predictor of atherogenicity. The serum concentrations of remnant-like particle triglyceride (RLPTG) and remnant-like particle cholesterol (RLPC) have been determined in a representative sample of the Czech MONICA study (n = 285). The relationship was investigated between remnant particle triglyceride/cholesterol concentrations and polymorphisms in the genes APOC3 (−482C→T/3238C→G), APOE (ε2/ε3/ε4), APOCI (−317-321ins), APOB (signal peptide), hepatic lipase (LIPE, −480C→T), and lipoprotein lipase (LPL, S447X). Univariate analysis showed significant effects on RLPTG associated only with the APOE genotype (P = 0.009), the APOC3 −482C→T genotype (P = 0.018), and the APOCI −317-321ins (P = 0.014) genotype and significant effects on RLPC with APOE (P = 0.01) and APOCI −317-321ins (P = 0.021). The raising effect of the APOE genotype for both remnant cholesterol and triglyceride was confined to the ε2/4 (n = 6) and ε4/4 (n = 3) groups, and thus when the ε2/4 group was omitted in order to analyze by allele (ε2+/ε3+/ε4+), significance was lost (P = 0.6). There was strong linkage disequilibrium between the APOE and APOCI alleles (χ2, P < 0.001) and a multivariate ANOVA of RLPTG with all three significantly associated variants as factors demonstrated that while the APOC3 −482C→T effect was independent of the others (P = 0.003), the APOCI −317-321ins and APOE effects were not. This was also true for the APOCI −317-321ins and APOE effects on RLPC. To assess whether APOE-CI effects on RLPC were independent of their effects on total cholesterol and triglyceride levels, multiple linear regression was used. Using multiple linear regression, it appeared that the APOE-CI effects on RLPC were independent of their effects on plasma cholesterol, but the effects of APOC3 and APOE-CI on RLPTG could not be separated from their effects on plasma Tg levels.Further characterization of this remnant particle phenotype and its genetic determinants may lead to a better understanding of its metabolism and contribution to atherosclerosis.