Search

Background: During pregnancy, serum cholesterol (TC) and triglyceride (TG) concentrations are known to increase significantly, but whether remnant lipoprotein particles (RLP) increase has not been shown. Methods: We compared lipid profiles in 22 healthy pregnant women to 31 healthy nonpregnant women and 24 patients with diabetes mellitus (DM), by measuring cholesterol and TG concentrations in major lipoprotein classes after HPLC separation and immunoseparation of RLP. Results: Serum TG and TC concentrations were significantly higher in the pregnant group than in the healthy control or DM groups. Cholesterol and TG concentrations of all major lipoprotein classes were also significantly higher in the pregnant group than the control and DM groups, except for VLDL-TG in the DM group. RLP-C and RLP-TG concentrations were significantly higher in the pregnant group (8.7 mg/dl and 25.4 mg/dl on average) than the control group (2.4 mg/dl and 5.7 mg/dl), but not different from the DM group (8.8 mg/dl and 24.1 mg/dl). RLP-TG to RLP-C ratios were similar among the three groups and correlated with the VLDL-TG to VLDL-C ratio. The percentages of RLP-C in VLDL-C and RLP-TG in VLDL-TG in the pregnant group (15.9% and 15.7%) were significantly lower than those of the control (48.5% and 35.6%) and the DM (32.7% and 20.8%) groups. Conclusions: RLP increased moderately during gestation with the increase in VLDL and TG, but the percentage of RLP in VLDL was significantly lower in the pregnant women compared with the control and DM patients, suggesting that hypertriglyceridemia in pregnancy is not primarily due to an increase in the atherogenic RLP. [Copyright &y& Elsevier]

Fourier-transform infrared (FT-IR) spectroscopy was applied to examine human serum very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) in aqueous solution and in solid film for characterizing lipid components. On the basis of the FT-IR second-derivative spectra for standard samples of triglycerides, cholesterol esters and phospholipids, it was found that the band at 1746 cm−1 for VLDL and the band at 1738 cm−1 for LDL were mainly due to the unsaturated triglycerides and unsaturated cholesterol esters, respectively. The implications of ester C&z.dbnd6;O stretching bands are discussed. [Copyright &y& Elsevier]

Abstract: Aim: This epidemiological study was done to generate normal ranges for the cholesterol and triglyceride levels in serum lipoprotein subclasses isolated from healthy adults based on gender and menopausal status. Methods: Cholesterol and triglyceride levels in 20 lipoprotein subclasses as separated by high performance liquid chromatography were measured in serum obtained from 825 fasting healthy subjects (267 men, 558 women). Results: For serum cholesterol, 13.7% was found in very low density lipoprotein (VLDL) subclasses, 55.6% in low density lipoprotein (LDL) subclasses, and 30.4% in high density lipoprotein (HDL) subclasses. For serum triglycerides, these values were 52.1%, 27.9%, and 17.4%, respectively. Levels of cholesterol in some VLDL subclasses were inversely correlated with the levels of some HDL subclasses, while for triglycerides, elevated levels in any one subclass were generally strongly associated with elevated levels in all other subclasses. Men had significantly higher large VLDL-cholesterol levels than women (P < 0.05), while women had significantly higher small VLDL-cholesterol levels than men (P < 0.001). Women had significantly higher large LDL- and large and medium HDL-cholesterol levels than men (P < 0.001). Men had significantly higher chylomicron (CM), large and medium VLDL-, and small LDL-triglyceride levels than women (P < 0.001). Women had significantly higher very large and large HDL-triglyceride levels than men (P < 0.01). Postmenopausal women had significantly higher CM, all VLDL, and large, medium and small LDL-cholesterol levels, and significantly higher all VLDL, LDL, and HDL-triglyceride levels than premenopausal women (P < 0.001). Conclusions: Our data document important gender and menopausal status differences in cholesterol and triglyceride subclass levels, as well as significant correlations between values in the various serum lipoprotein subclasses. [Copyright &y& Elsevier]

Abstract: Objectives: To evaluate the gel permeation high-performance liquid chromatography (GP-HPLC) method for determination of triglyceride (TG) levels in low-density lipoprotein (LDL) and high-density lipoprotein (HDL). Design and methods: The GP-HPLC and the ultracentrifugation(UC)/precipitation methods were used and compared. Results: There was no significant difference in measured levels of LDL-triglyceride between the two methods, but the HDL-triglyceride levels measured by the GP-HPLC technique were significantly higher than the UC/precipitation one (145±47 mg/L and 121±45 mg/L respectively, n =38, p <0.0001). Conclusions: A GP-HPLC technique provides LDL-TG levels comparable to those obtained by the UC/precipitation method. [Copyright &y& Elsevier]

Abstract: Probucol is a unique hypolipidemic agent that increases cholesteryl ester transfer protein (CETP) activity. Enhanced CETP-mediated conversion of high-density lipoprotein (HDL) partly explains the probucol-induced decrease in HDL cholesterol and increase in plasma preβ1-HDL (native lipid-poor HDL) concentrations. However, HDL cholesterol is reduced in patients that are completely deficient in CETP. Angiopoietin-like protein 3 (ANGPTL3) is an endogenous suppressor of endothelial lipase that promotes the hydrolysis of HDL phospholipids and may generate preβ1-HDL. To determine whether probucol decreases ANGPTL3 and HDL phospholipids while increasing preβ1-HDL, we measured these parameters before and after a 4-week probucol treatment in 39 hypercholesterolemic patients and age- and sex-matched controls. The median ANGPTL3 had decreased from 143 to 113μg/L by week 4 (p <0.05). High-performance liquid chromatography revealed that probucol decreased the phospholipid content of very large (13.5–15nm) and large (12.1nm) HDL particles predominantly by 65% (p <0.01) and 53% (p <0.001), respectively. The change in ANGPTL3, but not CETP mass, was positively correlated with that in large HDL phospholipids (r =0.455, p <0.05). The absolute and relative concentrations of preβ1-HDL increased by 14% (p <0.01) and 60% (p <0.001), respectively. The conversion rate of preβ1-HDL into α-migrating HDL by lecithin-cholesterol acyltransferase did not change significantly. In conclusion, probucol decreases plasma ANGPTL3 and HDL phospholipids while increasing preβ1-HDL. We speculate that probucol induces HDL remodeling via an endothelial lipase-mediated pathway. [Copyright &y& Elsevier]

Abstract: Objective: Coronary arteriosclerotic heart disease frequently develops in patients with diabetes. Decreased serum high-density lipoprotein cholesterol concentration and low-density lipoprotein (LDL) particle size, accompanied by hypertriglyceridemia, are associated with the onset of atherosclerosis. We recently reported that hypertriglyceridemia was significantly improved in patients with type 2 diabetes who ingested diacylglycerol (DAG) oil. The effect on variables, including LDL particle size related to lipid metabolism, however, was not examined. The present study investigated the effects on these variables in more detail. Methods: Patients with type 2 diabetes (n = 24) were assigned to receive DAG oil or triacylglycerol oil, and a 3-mo, single-blind, controlled study was performed. Patients replaced cooking oil in their daily diet with DAG or triacylglycerol oil, and anthropometry and blood sampling were performed at monthly intervals. Results: There were no significant differences in calorie intake or amount of test oil ingested between groups. Waist circumference and serum triacylglycerol concentrations were significantly lower and serum concentrations of high-density lipoprotein cholesterol and apolipoprotein-AI were significantly higher in the DAG oil group than in the triacylglycerol oil group. Plasma plasminogen activator inhibitor-1 concentrations were significantly lower in the DAG oil group. LDL particle size tended to increase in the DAG oil group and was significantly larger in patients who had a small initial LDL particle size (<25.5 nm). There were no significant differences in variables related to glucose metabolism or in serum concentration of free fatty acids or total ketone bodies. Conclusions: These results indicate that DAG oil may be useful for patients who have type 2 diabetes in the management of obesity and lipid abnormalities. [Copyright &y& Elsevier]

Although the anti-inflammatory effect of interleukin-1 (IL-1) receptor antagonist (IL-1Ra) has been described, the contribution of this cytokine to cholesterol metabolism remains unclear. Our aim was to ascertain whether deficiency of IL-1Ra deteriorates cholesterol metabolism upon consumption of an atherogenic diet. IL-1Ra-deficient mice (IL-1Ra-/-) showed severe fatty liver and portal fibrosis containing many inflammatory cells following 20 weeks of an atherogenic diet when compared with wild type (WT) mice. Expectedly, the levels of total cholesterol in IL-1Ra mice were significantly increased, and the start of lipid accumulation in liver was observed earlier when compared with WT mice. Real-time PCR analysis revealed that IL-1Ra-/- mice failed to induce mRNA expression of cholesterol 7α-hydroxylase, which is the rate-limiting enzyme in bile acid synthesis, with concurrent up-regulation of small heterodimer partner 1 mRNA expression. Indeed, IL-1Ra-/- mice showed markedly decreased bile acid excretion, which is elevated in WT mice to maintain cholesterol level under atherogenic diet feeding. Therefore, we conclude that the lack of IL-1Ra deteriorates cholesterol homeostasis under atherogenic diet-induced inflammation. [ABSTRACT FROM AUTHOR]

Hitherto triglycerides (TG) and TG-rich lipoproteins were been of limited value as surrogates for antemortem levels. We measured TG levels in postmortem plasma from sudden coronary death cases (SCD, n=91) by using two TG assays, Dry Chem TG (free glycerol was added) and the Determiner L-TG (without added free glycerol) that measured net TG. TG levels were markedly higher by the Dry Chem TG (y) vs. Determiner L-TG (x), y=1.03x+229 mg/dl. HPLC showed large amounts of free glycerol in postmortem plasma and in TG-rich lipoprotein remnants (RLP). These results were verified in a rabbit model of SCD. Further, RLP from SCD were found to be biophysically similar to those from living patients with coronary artery disease (CAD). In conclusion, postmortem plasma sampled up to 12 h after death is appropriate for measuring lipid and lipoproteins, TG and RLP-TG as surrogates for antemortem levels when a TG assay without added free glycerol is used. [Copyright &y& Elsevier]

Hormone-sensitive lipase (HSL) plays a crucial role in the hydrolysis of triacylglycerol and cholesteryl ester in various tissues including adipose tissues. To explore the role of HSL in the metabolism of fat and carbohydrate, we have generated mice lacking both leptin and HSL (Lepob/ob/HSL-/-) by cross-breeding HSL-/- mice with genetically obese Lepob/ob mice. Unexpectedly, Lepob/ob HSL-/- mice ate less food, gained less weight, and had lower adiposity than Lepob/ob/HSL+/+ mice. Lepob/ob HSL-/- mice had massive accumulation of preadipocytes in white adipose tissues with increased expression of preadipocyte-specific genes (CAAT/enhancer-binding protein β and adipose differentiation-related protein) and decreased expression of genes characteristic of mature adipocytes (CCAAT/enhancer-binding protein α, peroxisome proliferator activator receptor γ, and adipocyte determination and differentiation factor 1/sterol regulatory element-binding protein-1). Consistent with the reduced food intake, hypothalamic expression of neuropeptide Y and agouti-related peptide was decreased. Since HSL is expressed in hypothalamus, we speculate that defective generation of free fatty acids in the hypothalamus due to the absence of HSL mediates the altered expression of these orexigenic neuropeptides. Thus, deficiency of both leptin and HSL has unmasked novel roles of HSL in adipogenesis as well as in feeding behavior. [ABSTRACT FROM AUTHOR]

High-density lipoprotein (HDL) plays an important role in reverse cholesterol transport by removing accumulated cholesterol from extrahepatic tissues. Subsequently, cholesterol ester (CE) on HDL in humans is transported to apolipoprotein B-containing lipoproteins by cholesteryl ester transfer protein (CETP). CETP deficiency, which is common in the Japanese population, leads to a marked increase in HDL-cholesterol levels due to impaired CE transport from HDL to LDL. It has been reported that the HDL observed in CETP deficiency is an atherogenic lipoprotein, as it contains a large amount of CE. Scavenger receptor class B type I (SR-BI) has been found to be an authentic HDL receptor that mediates the selective uptake of HDL CE and the bi-directional transfer of free cholesterol between HDL and cells. In the present study, the interaction between SR-BI and CE-rich HDL from CETP-deficient patient was studied in order to evaluate the anti-atherosclerotic role of SR-BI in relation to CE uptake and reverse cholesterol transport. When CE-rich HDL was added to the medium of SR-BI-transfected CHO (SR-BI CHO) cells, more CE accumulated in SR-BI CHO cells compared to control HDL. In contrast, the amount of cholesterol efflux from SR-BI CHO cells into HDL was almost the same between the two HDLs. Therefore, when CE-rich HDL was added to the medium of SR-BI CHO cells, the intracellular CE content increased significantly. Moreover, the particle size of HDL in CETP-deficient patient decreased significantly when the HDL was added to the medium of SR-BI CHO cells, and this HDL showed an increment of CE efflux from foam cells. These results indicate that SR-BI reduces the cholesterol content and size of the CE-rich HDL from CETP deficiency, which ultimately activate reverse cholesterol transport system. [Copyright &y& Elsevier]

Demonstrates that low-density lipoprotein receptor-related protein 5 (LRP5) is required for normal cholesterol metabolism and glucose-induced insulin secretion. Comparison of plasma proteins in mice lacking LRP5; Absence of significant effects in the sole LPR5 deficiency; Mediation of both apolipoprotein E-dependent and apolipoprotein E-independent catabolism of plasma lipoproteins by LRP5.

• New equation to calculate sdLDL cholesterol is validated by HPLC analysis. • Ultracentrifugal preparation underestimates VLDL comparing to HPLC. • Homogeneous HDL cholesterol assay is validated by HPLC analysis. [ABSTRACT FROM AUTHOR]