BACKGROUND

Cholesterol levels of non-high-density lipoprotein (non-HDL), which contains low-density lipoprotein (LDL), intermediate-density lipoprotein (IDL), very low-density lipoprotein (VLDL) and chylomicron (CM) remnant, have been proven to perform a significant predictor of coronary heart disease (CHD) better than LDL-cholesterol regardless of triglyceride (TG) levels. The present study investigated the relevance of TG-rich lipoproteins (IDL, VLDL, CM) to Framingham risk score (FRS) predictive of 10-year CHD risk.

METHODS

Lipoprotein profiles (cholesterol levels of HDL, LDL, IDL, VLDL, CM) in Japanese men (n = 487) who underwent medical check-up were determined by using our developed anion-exchange high performance liquid chromatography (AEX-HPLC). Total-cholesterol (TC), TG, fasting blood sugar (FBS) and hemoglobin (Hb) A1c were measured by routine methods. The lipoprotein profiles, non-HDL-cholesterol, TC, and TG were examined on these associations with FRS.

RESULTS

The lipid levels except for CM-cholesterol were significantly different between two groups (low FRS, < 10%; high FRS, ≥10%) (P < 0.0001), and body mass index (BMI), TC, TG, IDL-, and VLDL-cholesterol were significantly and positively correlated with FRS. Among them, the significant association of non-HDL-cholesterol to FRS was noted (r = 0.411, P < 0.0001). Multiple stepwise regression analysis shows that, in addition to non-HDL-cholesterol, IDL-cholesterol in TG-rich lipoproteins was significantly correlated with FRS in independently of BMI. These correlation results were similarly found even when the part of the study subjects (n = 348) without the drug therapy for hyperlipidemia, diabetes, and hypertension was investigated.

CONCLUSIONS

These results suggest that IDL-cholesterol may serve as a useful marker for CHD risk in Japanese men with increased non-HDL-cholesterol.

Background: Obesity has been suggested to be well correlated with altered levels of complete blood count (CBC) parameters. In this study, the relationship of body mass index (BMI) and circulating leptin levels with CBC among obese and overweight adults was examined. Methods: CBC and biochemical parameters, WBC and hematological profiles, leptin levels, related factors to liver, and kidney and lipid profiles were measured among 184 obese and overweight people aged 18-60 years. Statistical analysis was performed using SPSS software. To assess the normality of data, the Kolmogorov-Smirnov test was used. Logarithmic transformation was performed for some variables with non-normal distribution. The association between 2 quantitative variables was measured using bivariate correlation (Pearson or Spearman). Pearson correlations and multiple regression analysis were performed to assess the correlation between variables. Simple and multiple regression analyses were performed to predict some variables. P- value <0.05 was considered significant. Results: Hematocrit, insulin, fasting blood sugar, uric acid, TG, LDL-C, VLDL-C, and ALT were positively correlated with BMI (p=0.041, r=0.149 for hematocrit; p≤0.001, r=0.520 for insulin; p≤0.001, r=0.363 for FBS; p≤0.001, r=0.309 for uric acid; p=0.015, r=0.189 for TG; p=0.030, r=161 for LDL-C; p=0.019, r=0.181 for VLDL-C; p≤0.001, r=0.299 for ALT), whereas urea and HDL-C were negatively correlated with BMI (p≤0.001, r=-0.368 for urea; p≤0.001, r=-0.297 for HDL-C). Moreover, LDL-C and insulin were positively correlated with leptin (P = 0.011, r = 0.194 for LDL-C, P = 0.013, r = 0.114 for insulin) and hematocrit, urea, creatinine, TG and VLDL-C were negatively correlated with leptin (p=0.040, r=-0.162 for hematocrit; p≤0.001, r=-0.305 for urea; p=0.007, r=-0.219 for creatinine; p=0.025, r=0.188 for TG; p=0.007, r=-0.218 for VLDL-C). Our analysis showed that white blood cell was positively correlated with leptin (β=17.36, p=0.048). Also, other CBC parameters had no significant correlations with BMI and leptin. Conclusion: According to the findings of this study, BMI had a negative association with urea and HDL-C, while BMI had a positive association with insulin, hematocrit, FBS, uric acid, TG, VLDL-C, LDL-C, and ALT. Furthermore, leptin had a negative association with hematocrit, creatinine, and urea, TG, VLDL-C and a positive association with LDL-C and insulin among the participants of this study.

BACKGROUND

Patients with chronic kidney disease (CKD) have an increased risk for cardiovascular events (CVE). Uraemic dyslipidaemia, which is characterized by low HDL-cholesterol (HDL-C) and elevated triglycerides' levels, may contribute to this elevated cardiovascular risk. Cholesteryl ester transfer protein (CETP) lowers HDL-C by transferring cholesterol esters to LDL and VLDL particles. We tested the hypothesis that CETP activity is associated with CVE in patients with CKD stage V.

METHODS

We measured CETP activity and cholesterol levels in 69 haemodialysis patients. CVE and death were prospectively assessed over a follow-up period of 48 months.

RESULTS

CETP activity was negatively correlated with HDL-C levels in patients without lipid-lowering medication (r = -0.379, P = 0.005). We found no difference in CETP activity in patients with cardiovascular disease at baseline compared to patients without cardiovascular disease. The same was true for incident CVE during the follow-up. When stratifying patients by median CETP activity, patients with high CETP activity did not have an increased risk for CVE (P = 0.901 by the log-rank test) or death (P = 0.615). Similarly, after stratifying patients by median HDL-C no increased risk for CVE (P = 0.780) or death (P = 0.838) was found in patients with low HDL-C.

CONCLUSIONS

In summary, although CETP activity correlated with HDL-C levels, neither high CETP activity nor low HDL-C was associated with CVE in CKD stage V patients. Thus, pharmacological modification of HDL-C by CETP inhibitors seems to be of questionable value in these patients.

The objective of this work was to evaluate the associations between levels of endogenous sex hormones in women at midlife and lipoprotein subclasses. One hundred and twenty women (68 late peri-/postmenopausal and 52 pre-/early perimenopausal) from the Study of Women's Health Across the Nation (Pittsburgh site) were included. Lipoprotein subclasses were quantified using NMR spectroscopy. Participants (57.5% White and 42.5% Black) were 50.4 ± 1.9 years old. Adjusting for age, race, cycle day of blood draw, BMI, physical activity, and alcohol consumption, a negative correlation was found between estradiol (E2) and medium-small LDL particle (LDL-P) concentration (ρ = -0.19, P = 0.04). Further, E2 was positively correlated with HDL particle (HDL-P) size (ρ = 0.22, P = 0.02). For sex hormone binding globulin (SHBG), independent negative correlation was found with total small LDL-P concentration. SHBG was also positively correlated with LDL-P and HDL-P sizes (P < 0.05 for all). For free androgen index (FAI), positive correlations were found with concentrations of total VLDL particles, total LDL-Ps, and total small LDL-Ps. Additionally, FAI was negatively correlated with large HDL-P concentration, and HDL-P and LDL-P sizes (P < 0.05 for all). Lower levels of E2 and SHBG, and higher levels of FAI were associated with a more atherogenic profile of lipoprotein subclasses. Sex hormone levels at midlife may increase women's risk of coronary heart disease.

<Abst<em>r</em>actText>Gut mic<em>r</em>obiota significantly impacts human health and is influenced by dieta<em>r</em>y changes. We evaluated the effects of diets natu<em>r</em>ally <em>r</em>ich in polyphenols (PP) and/o<em>r</em> long-chain n-3 polyunsatu<em>r</em>ated fatty acids (LCn3) on mic<em>r</em>obiota composition in an ancilla<em>r</em>y analysis of a <em>r</em>andomized cont<em>r</em>olled t<em>r</em>ial in individuals at high ca<em>r</em>diometabolic <em>r</em>isk.</Abst<em>r</em>actText><Abst<em>r</em>actText>Seventy-eight individuals with high waist ci<em>r</em>cumfe<em>r</em>ence and at least one additional component of the metabolic synd<em>r</em>ome we<em>r</em>e <em>r</em>andomized to an isoene<em>r</em>getic 8-week diet: (a) low LCn3 and PP; (b) high LCn3; (c) high PP; o<em>r</em> (d) high LCn3 and PP. Mic<em>r</em>obiota analysis was pe<em>r</em>fo<em>r</em>med on feces collected befo<em>r</em>e and afte<em>r</em> the inte<em>r</em>vention. DGGE analysis of the p<em>r</em>edominant bacte<em>r</em>ia, Eubacte<em>r</em>ium <em>r</em>ectale and Blautia coccoides g<em>r</em>oup (Lachnospi<em>r</em>aceae, EREC), Clost<em>r</em>idium leptum (Ruminococcaceae, CLEPT), Bacte<em>r</em>oides spp., Bifidobacte<em>r</em>ia, and Lactobacillus g<em>r</em>oup was pe<em>r</em>fo<em>r</em>med. A quantitative <em>r</em>eal-time PCR was pe<em>r</em>fo<em>r</em>med fo<em>r</em> the same g<em>r</em>oup, additionally including Atopobium cluste<em>r</em> (Co<em>r</em>iobatte<em>r</em>iaceae). Befo<em>r</em>e and afte<em>r</em> the inte<em>r</em>vention, pa<em>r</em>ticipants unde<em>r</em>went a 75 g OGTT and a high-fat test meal to evaluate glucose and lipid <em>r</em>esponse.</Abst<em>r</em>actText><Abst<em>r</em>actText>Adhe<em>r</em>ence to the fou<em>r</em> diets was optimal. PP significantly inc<em>r</em>eased mic<em>r</em>obial dive<em>r</em>sity (p = 0.006) and CLEPT (p = 0.015), while it <em>r</em>educed EREC (p = 0.044). LCn3 significantly inc<em>r</em>eased the numbe<em>r</em>s of Bifidobacte<em>r</em>ia (p = 0.041). Changes in CLEPT numbe<em>r</em>s co<em>r</em><em>r</em>elated with changes in ea<em>r</em>ly insulin sec<em>r</em>etion (<em>r</em> = 0.263, p = 0.030). Changes in Atopobium numbe<em>r</em>s co<em>r</em><em>r</em>elated with postp<em>r</em>andial t<em>r</em>iglyce<em>r</em>ides in plasma (<em>r</em> = 0.266, p = 0.026) and la<em>r</em>ge <em>VLDL</em> (<em>r</em> = 0.313, p = 0.009), and choleste<em>r</em>ol in la<em>r</em>ge <em>VLDL</em> (<em>r</em> = 0.319, p = 0.008).</Abst<em>r</em>actText><Abst<em>r</em>actText>Diets natu<em>r</em>ally <em>r</em>ich in PP o<em>r</em> LCn3 influenced gut mic<em>r</em>obiota composition in individuals at high ca<em>r</em>diometabolic <em>r</em>isk. These modifications we<em>r</em>e associated with changes in glucose/lipid metabolism.</Abst<em>r</em>actText>

Flax oil feeding has been proposed to have beneficial effects on the outcome of the metabolic syndrome due to the high n-3 fatty acid content of flax oil; however, the mechanisms of its action remain largely unknown. We investigated the effects of flax oil feeding on hyperlipidaemia, hyperglycaemia, hepatic steatosis and oxidative stress in the spontaneously hypertensive (SHR)/NDmcr-cp rats, a genetic model of the metabolic syndrome. Hepatic gene expression of PPAR-α, PPAR-γ and sterol-regulatory element-binding protein-1c was also assessed in order to investigate the possible underlying mechanisms. Obese and lean SHR/NDmcr-cp rats were fed high-fat diets enriched with either lard or flax oil for a period of 4 weeks. Obese rats exhibited higher body weight, liver weight and mesenteric fat-, epididymal fat- and renal fat-pad weights, and also TAG and cholesterol concentrations in serum and VLDL, LDL and HDL fractions, when compared with the lean rats (P < 0·001), irrespective of the diets. Concentrations of fasting serum insulin and urinary thiobarbituric acid reactive substances were lower in flax oil-fed obese (FO) rats compared with the lard-fed obese (LO) rats (P < 0·01). Flax oil feeding also revealed a significant reduction in hepatic TAG and cholesterol concentrations in obese rats compared with the LO rats (P < 0·05). In addition, FO rats exhibited significantly higher hepatic mRNA expression of PPAR-γ, which negatively correlated (r - 0·98, P < 0·05) with their hepatic lipid levels. These findings suggest that flax oil feeding may activate PPAR-γ-dependent pathways to alter the hepatic lipid metabolism and to increase insulin sensitivity in the obese SHR/NDmcr-cp rats.

The aim of this study is to determine oxidative protein and lipid damage in adult hypopituitary GH-deficient patients. Eighteen hypopituitary GH-deficient--otherwise healthy-adults on conventional replacement therapy other than GH (9 male, 9 female, age 41.8 +/- 16.4 yr) and 18 healthy subjects (6 male, 12 female, age 40.3 +/- 16.2 yr) participated in the study. Plasma products of oxidative protein damage [protein carbonyl (PCO) and nitrotyrozine (NT)], plasma oxidized LDL (oxLDL), plasma product of oxidative lipid damage [lipid hydroperoxide (LHP)] and antioxidant status of the plasma [total thiol (T-SH)] were measured. Body fat percentage, total and LDL-cholesterol concentrations were significantly higher in the hypopituitary group. Plasma PCO, NT, LHP and T-SH concentrations did not differ significantly between patients and controls. OxLDL concentration was significantly higher in the hypopituitary patients (62.4 +/- 17.8 vs 43.1 +/- 11.3 U/l, p = 0.001). In the patients, oxLDL correlated significantly with the duration of hypopituitarism (r = 0.6323, p = 0.01). In the controls, oxLDL correlated significantly with blood pressure, total and VLDL-cholesterol concentrations. Increased oxLDL concentration may indicate increased oxidative stress within the vascular compartment and may contribute to the proatherogenic state in GH-deficient hypopituitary patients independent from conventional risk factors.

We identified syntaxin 5 (Stx5), a protein involved in intracellular vesicle trafficking, as a novel interaction partner of the very low density lipoprotein (VLDL)-receptor (VLDL-R), a member of the LDL-receptor family. In addition, we investigated the effect of Stx5 on VLDL-R maturation, trafficking and processing. Here, we demonstrated mutual association of both proteins using several in vitro approaches. Furthermore, we detected a special maturation phenotype of VLDL-R resulting from Stx5 overexpression. We found that Stx5 prevented advanced Golgi-maturation of VLDL-R, but did not cause accumulation of the immature protein in ER, ER to Golgi compartments, or cis-Golgi ribbon, the main expression sites of Stx5. Rather more, abundantly present Stx5 was capable of translocating ER-/N-glycosylated VLDL-R to the plasma membrane, and thus was insensitive to BFA treatment and low temperature. Furthermore, abundant presence of Stx5 significantly interfered with VLDL-R reaching the trans-Golgi network. Based on our findings, we postulate that Stx5 can directly bind to the C-terminal domain of VLDL-R, thereby influencing the receptor's glycosylation, trafficking and processing characteristics. Resulting from that, we further suggest that Stx5 might play a role in modulating VLDL-R physiology by participating in an abrasively described or completely novel Golgi-bypass pathway.

(R)- α -lipoic acid (ALA), an essential cofactor in mitochondrial respiration and a potential antioxidant, possesses a wide array of metabolic benefits including anti-obesity, glucose lowering, insulin-sensitizing, and lipid-lowering effects. In this study, the curative effects of ALA (100 mg/kg) on a spectrum of conditions related to metabolic syndrome and type 2 diabetes (T2D) were investigated in a high-fat diet (HFD)-fed and low-dose streptozotocin (STZ)-induced rat model of metabolic syndrome and T2D. The marked rise in the levels of glucose, triglycerides, total-cholesterol, LDL-cholesterol, and VLDL-cholesterol in the blood of HFD-fed and low-dose STZ-injected rats were significantly reduced by ALA treatment. Furthermore, ALA treatment significantly increased the serum HDL-cholesterol levels and tended to inhibit diabetes-induced weight reduction. Mathematical computational analysis revealed that ALA also significantly improved insulin sensitivity and reduced the risk of atherosclerotic lesions and coronary atherogenesis. This study provides scientific evidence to substantiate the use of ALA to mitigate the glucose and lipid abnormality in metabolic syndrome and T2D.

BACKGROUND

The objective of the study was to examine post hoc associations between plasma sphingolipids and lipoprotein kinetics in men with the metabolic syndrome after rosuvastatin treatment.

METHODS

Plasma sphingolipid profiling, determined by tandem mass spectrometry, was performed in a randomized, double-blind, triple-crossover trial (n = 12) of 5-week treatment periods with placebo or rosuvastatin (10 or 40 mg/d) with 2-week washouts between treatments.

CONCLUSIONS

Baseline plasma ceramides were associated with very low-density lipoprotein (VLDL) apolipoprotein (apo)-B-100 concentration (r = 0.58, P < .05) and inversely with VLDL apoB-100 fractional catabolic rate (FCR; r = -0.67, P = .02). Posttreatment changes with rosuvastatin (40 mg/d) in plasma ceramides were inversely associated with VLDL apoB-100 FCR (r = -0.62, P = .03) independent of changes in plasma triglycerides, cholesterol, and low-density lipoprotein-cholesterol. By contrast, baseline and postrosuvastatin treatment plasma sphingomyelin levels were not associated with apoB-100 kinetics. Plasma ceramides and sphingomyelin were not associated with the kinetics or concentrations of high-density lipoprotein apoA-I, and low-density lipoprotein apoB. In the metabolic syndrome, the ability of rosuvastatin to increase VLDL apoB-100 FCR may reflect ceramide-specific mechanistic actions and/or sphingolipid exchange.

To identify the substrate specificity of lipoprotein lipase (LPL) for triacylglycerol-rich lipoproteins with monoacid-rich triacylglycerols, monoacid-rich lipoproteins were prepared and kinetic parameters of LPL were characterized. Male broiler chickens were fed 8 g/100 g fat diets differing only in the fat source: palm oil (tripalmitin-rich), olive oil (triolein-rich), safflower oil (trilinolein-rich) and linseed oil (trilinolenin-rich). After diets were fed for 3 d, chickens were starved for 2 d and then force-fed emulsions containing one of the monoacid-triacylglycerols: tripalmitin, triolein, trilinolein or trilinolenin. The triacylglycerols in chylomicrons and very low density lipoprotein (VLDL) of chickens force-fed tripalmitin, triolein or trilinolein contained the corresponding acid at more than 70% of total acids. Linolenic acid was incorporated into chylomicrons and VLDL to a lower extent (51.2 and 57.2%, respectively) in chickens force-fed trilinolein. Major apolipoproteins and lipid compositions were not significantly different among all lipoproteins isolated from chickens fed the different fats. Vmax of LPL was significantly higher (P < 0.05) for palmitic acid-rich chylomicrons and VLDL and decreased with increasing chain length and unsaturation of monoacid: 16:0>18:1>18:2>18:3. The electron spin resonance analysis, order parameter (S), decreased with monoacid chain length and unsaturation. In addition, the Vmax of LPL increased linearly (P < 0.01, r = 0. 912) with an increase in the palmitic acid content of the lipoprotein triacylglycerols. These findings suggest that lipoprotein catalysis by LPL is modulated by the palmitic acid content of the lipoprotein triacylglycerol, which affects the fluidity of lipoproteins.

The aim of the study is to investigate serum lipoproteins abnormalities including low-density lipoprotein (LDL) particle size, and their relationship with other cardiovascular risk factors in men with essential hypertension. Plasma glucose and serum insulin levels during oral glucose tolerance test (OGTT), serum lipoprotein(a), apolipoprotein (apo) A-I. apo B. cholesterol and triglycerides in serum and in lipoproteins, and LDL particle diameter were measured in thirty-eight consecutive newly-diagnosed non-diabetic untreated hypertensive men and 38 healthy male controls. Plasma glucose at baseline, 60 and 120 min during OGTT was significantly higher in patients than controls whereas serum insulin levels did not differ between patients and controls. Serum apo B and triglycerides were significantly raised in patients compared with controls (1.08 +/- 0.17 g/L [mean +/- SD] vs 0.97 +/- 0.22 g/L. p < 0.05, and 1.56 +/- 0.90 mmol/L vs 1.15 +/- 0.57 mmol/L, p < 0.05, respectively). Very-low-density lipoprotein (VLDL) triglycerides and LDL-cholesterol were increased in patients compared with controls (0.89 +/- 0.79 mmol/L and 0.54 +/- 0.35 mmol/L, p < 0.05, and 4.08 +/- 0.85 mmol/L and 3.60 +/- 0.92 mmol/L, p < 0.05, respectively) whereas high-density lipoprotein (HDL) cholesterol was lower in patients compared with controls 0.95 +/- 0.22 mmol/L and 1.07 +/- 0.20 mmol/L, p < 0.05). Adjustment for body mass index, abdominal/hip perimeter ratio and area under the glucose curve did not attenuate the relationship between hypertension and VLDL-triglycerides. Six patients and two controls had a mean LDL diameter < or = 25.5 nm and in the former serum triglycerides ranged from 1.86 mmol/L to 2.37 mmol/L. Mean LDL particle diameter in both patients and controls showed an inverse relationship with log-transformed serum triglycerides (r = - 0.51, p < 0.001 and r = - 0.47, p < 0.005, respectively). Among patients, those with serum triglycerides>> or = [corrected] 1.58 mmol/L had a lesser mean LDL diameter than those with triglycerides above this threshold (25.78 +/- 0.47 nm vs 26.30 +/- 0.35 nm, p < 0.001). Higher plasma glucose, serum apo B and LDL-cholesterol as well as the decrease in serum HDL-cholesterol in patients with hypertension are consistent with high coronary heart disease risk. Not only mild hypertriglyceridemia but also high-normal serum triglycerides in themselves or as a surrogate of a predominance of small dense LDL particles in plasma convey an additional risk for cardiovascular disease in hypertensive patients even though routine plasma lipids are within or near normal range.

Dietary modifications including healthy eating constitute one of the first line strategies for prevention and treatment of atherosclerotic cardiovascular diseases (CVD), including atherosclerosis. In this study, we assessed anti-atherogenic effects of a combination of wild rice and phytosterols in low-density lipoprotein receptor knockout (LDL-r-KO) mice. Male LDL-r-KO mice were divided into four groups and fed with: (1) control diet; (2) the control diet containing 60% (w/w) wild rice; (3) the control diet containing 2% (w/w) phytosterols; or (4) the control diet containing both wild rice and phytosterols for 20weeks. All diets were supplemented with 0.06% (w/w) dietary cholesterol. Blood samples, hearts, and feces were collected and used for biochemical and histological examination. Consumption of 60% (w/w) wild rice in combination with 2% (w/w) phytosterols significantly reduced the size and severity of atherosclerotic lesions in the aortic roots as compared to those in the control group. This effect was associated with significant reductions in plasma total, LDL and VLDL cholesterol concentrations as well as an increase in fecal cholesterol excretion. In conclusion, the dietary combination of wild rice and phytosterols prevents atherogenesis in this animal model. Further investigations are needed to understand mechanisms of action and potential clinical outcome of such dietary intervention.

The very low density lipoprotein receptor gene (VLDL-R) is a receptor for apolipoprotein-epsilon (APOE)-containing lipoproteins, and thus has been suggested as a possible risk factor for Alzheimer disease (AD). Recently, Okuizumi et al. [Nature Genet, II (1995) 207-209] reported an association between the 96 bp allele at the VLDL-R locus and AD in a Japanese population. The association resulted in a two-fold increase of risk that decreased with increasing age. We have examined this association in 316 Caucasian sporadic AD patients, comparing their findings to 160 Caucasian AD spouse controls. We also investigated 53 late-onset Caucasian AD families for association and linkage. Our data failed to confirm linkage and/or association to the VLDL-R locus. Stratification by age at onset or APOE genotype also failed to show significant results.

A group of 12 young NZW rabbits of the same breeding strain were fed a diet enriched with 0.1% cholesterol by weight. The resulting modest hypercholesterolaemia resolved after 4-5 months. Two animals that died during this period showed no gross or microscopic atherosclerosis. After 6 months, the dietary cholesterol was increased to 0.2%. In some animals this resulted in moderate hypercholesterolaemia. One animal that died at this time showed no atherosclerosis with a mean serum cholesterol level of 224 mg/dl. Just after one year, dietary cholesterol was increased to 0.3%. This resulted in definite hypercholesterolaemia in some animals, but a few resisted the treatment with mean serum cholesterol levels around 40-60 mg/dl. In general, animals with established hypercholesterolaemia showed severe atherosclerosis, but often of a more fibrous and less cellular nature than is usual in the rabbit. Aortic wall cholesterol content (on a weight basis) correlated positively with serum cholesterol concentration (r = + 0.69, P approximately 0.05) and negatively with the ratio of HDL cholesterol to (LDL plus VLDL) cholesterol (double log plot: r = -0.79, P less than 0.025).

It is now commonly known that possession of one of the three common alleles of the apolipoprotein E (APOE) gene (allele epsilon 4) confers an increased risk for both familial and sporadic Alzheimer's disease (AD), and that this risk is dose-dependent. Other genes that may play a role in AD, either through independent association with the disease or through modification of the existing APOE risk, are under investigation. One such gene, the very low density lipoprotein receptor (VLDL-R) gene, was reported by Okuizumi et al. to be independently associated with AD in a Japanese population, but not interactive with the APOE4 conferred risk. Their clinic-based data set demonstrated a 2-fold increased risk conferred by the 5-repeat allele of a polymorphism in VLDL-R. As recruitment from a clinic rather than a population-based sample may result in a distortion of allele frequencies, as has been shown with APOE allele frequencies, it is important to investigate this association in a population-based study. We have genotyped both population and clinic-based AD data sets at this VLDL-R polymorphism, and we find no independent association between the VLDL-R gene and the occurrence of AD in either sample. Further, despite the biochemical relationship between the VLDL-R and APOE proteins, we find no significant statistical interaction between the alleles at these loci.

The fluorescent phospholipid dansyl phosphatidylethanolamine (DPE) (dansyl, 5-dimethylaminonaphthalene-1-sulfonyl) was incorporated into very low density lipoproteins (VLDL) to form DPE-VLDL. The addition of milk lipoprotein lipase to DPE-VLDL in the presence of albumin resulted in a greater than 3-fold fluorescence increase and a 20 nm blue shift in the wavelength of the emission maxima of the dansyl fluorophore. The lipoprotein lipase-induced fluorescence changes occurred concomitantly with the release of free fatty acids from VLDL. Lipoprotein lipase did not produce fluorescence changes in DPE incorporated into either low or high density lipoproteins. The rate of fluorescence increase in DPE-VLDL was maximal at 37 degrees C, dependent on the concentration of lipoprotein lipase and VLDL, and followed typical Michaelis-Menten kinetics with a Km of 1.0 for lipoprotein lipase. Both the initial rate and the total fluorescence increase correlated well (r = 0.98 and 0.95) with the release of free fatty acids. We conclude that the lipoprotein lipase-induced fluorescence increases in DPE-VLDL provide an accurate, convenient, and the only noninvasive means of following continuously the lipolysis of human VLDL.

To assess whether the Lowry-tetramethylurea method for measuring apolipoprotein B-100 (apo-B) in very low density lipoprotein (VLDL) could be replaced by direct assay of VLDL apo-B using a highly practicable immunological method. Seventy five fasting blood samples were collected from patients attending the lipid clinic at this hospital. Plasma was separated immediately and VLDL isolated by preparative ultracentrifugation at solution density 0.93-1.006 kg/l. Apo-B was precipitated from an aliquot of the VLDL fraction using the tetramethylurea (TMU) technique and protein mass determined by the Lowry method (LM); mean apo-B 83.02 micrograms/ml (SD 74.85). Apo-B was also measured in VLDL using direct immunoturbidimetry on the Cobas-Fara analyser; mean apo-B 82.32 micrograms/ml (SD 72.88). There was a very close correlation between methods (immunoturbidimetry = 0.94.LM + 3.95, r = 0.97, p < 0.001). The mean difference between methods (constant error) was small (0.70 microgram/ml) and not significant (p = 0.742). Random error was 13.01 micrograms/ml by analysis of variance. It is concluded that immunoturbidimetry, a more rapid and convenient test, may replace the LM and TMU techniques for measuring VLDL apo-B concentration and that this method could be applied to research studies requiring analysis of large numbers of samples.

OBJECTIVE

Elevation of postprandial lipemia characterized by a rise in triglyceride (TG)-rich lipoproteins can increase the risk of atherogenesis. The objective of this study was to investigate postprandial lipemia response to a single dietary fat/sugar load test and monitor beneficial changes induced by the consumption of Platycodi radix (AP) beverage in healthy subjects.

METHODS

A total of 52 subjects were randomly assigned to either placebo or AP beverage group with a high-fat shake in a randomized controlled crossover trial. Postprandial blood was collected at 0, 1, 2, 4, and 6 h and analyzed for TG and lipoprotein lipase mass. Inhibition of pancreatic lipase was determined in vitro.

RESULTS

AP inhibited pancreatic lipase activity in vitro (IC50 = 5 mg/mL). Compared to placebo beverage, AP beverage consumption with a high-fat shake induced significant increase of plasma lipoprotein lipase mass (P = 0.0111, β estimate = 4.2948) with significant reduction in very low-density lipoprotein (VLDL) TG concentration (P = 0.038, β estimate = -52.69) at 6 h. Based on significant correlation between high-fat dietary scores MEDFICTS and postprandial TG responses in VLDL (P = 0.0395, r = 0.2127), subgroup analysis revealed that 6 h-postprandial VLDL TG response was significantly decreased by AP consumption in subjects with MEDFICTS ≥ 40 (P = 0.0291, β estimate = -7214).

CONCLUSIONS

AP beverage might have potential to alleviate postprandial lipemia through inhibiting pancreatic lipase activity and elevating lipoprotein lipase mass. Subgroup analysis revealed that subjects with high-fat dietary pattern could be classified as responders to AP beverage among all subjects.

Serum magnesium concentration (S-Mg) has been reported to be inversely associated with atherogenic lipid fractions and with blood glucose concentrations. In some studies on humans, oral magnesium supplementation has been found to improve the lipoprotein balance. Against this background the present study was undertaken to determine whether reductions in atherogenic lipid fractions are associated with S-Mg alterations. Total S-Mg was measured in 23 patients with non-insulin-dependent diabetes mellitus (NIDDM) treated with the lipid-lowering drugs gemfibrozil and simvastatin in a double-blind cross-over study. The mean S-Mg at the end of the initial placebo period, ie, before active treatment, was 0.80 (SD 0.06) mmol/L. Treatment with gemfibrozil 600 mg twice daily for 4 months decreased S-Mg by 0.02 mmol/L (P =.02), and treatment with simvastatin 10 mg daily for 4 months again decreased S-Mg by 0.02 mmol/L (P =.10; not significant [NS]) The changes in S-Mg during the 2 different treatment periods were closely correlated (r = 0.66, P <.001). Fasting plasma glucose concentrations increased significantly by 17% during both drug regimens. The changes in fasting plasma glucose and S-Mg were significantly correlated both during gemfibrozil treatment (r = -0.56, P <.01) and during treatment with simvastatin (r = -0.44, P <.05). Changes in glucose tolerance or insulin sensitivity did not correlate to changes in S-Mg. The associations between changes in serum very-low-density lipoprotein (VLDL) fractions and S-Mg did not reach statistical significance (r = -0.37, P <.10). Changes in low-density lipoprotein (LDL) cholesterol and S-Mg did not correlate. In conclusion, total S-Mg concentration decreased during treatment with gemfibrozil and simvastatin in patients with NIDDM. During both drug regimens changes in S-Mg status were inversely correlated to changes in plasma glucose concentrations, while changes in lipid status were not significantly correlated with changes in S-Mg.

BACKGROUND

Remnant lipoprotein (RLP), associated with atherosclerosis progression, is often elevated in diabetes mellitus. The RLP level is estimated by immune-separation method and agarose-gel electrophoresis (AGE).

METHODS

The patients were grouped into three groups according to tertile of RLP-cholesterol (RLP-C) levels. The lipoprotein profiles of type II diabetic patients (T2DM) (n=194) were measured by an anion-exchange liquid chromatography (AEX-HPLC) and an AGE with lipid-staining or cholesterol-staining.

RESULTS

IDL- and VLDL-cholesterol by the AEX-HPLC, and VLDL-levels by the AGE with lipid-staining and with cholesterol-staining were significantly different in the three groups. In all the subjects, IDL-cholesterol (r=0.531) and VLDL-cholesterol (r=0.880) by the AEX-HPLC method were strongly correlated with RLP-C, but only VLDL levels were correlated with RLP-C in AGE, respectively.

CONCLUSIONS

These results suggest that the AEX-HPLC, which can provide cholesterol levels of not only VLDL but also IDL, is helpful for estimation of lipid profiles in T2DM with high RLP-C.

Vitamin E is a lipid-soluble vitamin and an important antioxidant that protects lipoproteins and cell membranes from lipid peroxidation. The aims of the present study were to investigate, in patients with parenchymal liver cirrhosis, the following: (1) nutritional and vitamin E status in relation to compositional changes in lipoproteins; and (2) the effects of these alterations on the patients' plasma susceptibility to copper-mediated oxidation. Patients (n = 55) with liver cirrhosis and 25 healthy volunteers had vitamin E in serum and in isolated lipoprotein fractions analyzed by high-performance liquid chromatography (HPLC). Plasma susceptibility to peroxidation was measured by incubation with Cu(2+). Nutritional status was assessed by anthropometry. Vitamin E concentration was significantly decreased (P <.001) in the serum and in very-low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) in cirrhotic patients. The decrease was related to the degree of liver impairment. There were significant correlations between cholesterol and vitamin E concentrations in serum and in all the lipoprotein fractions (r between 0.72 and 0.89; P <.001) in cirrhotic patients, but there were no significant relationships between vitamin E and any of the anthropometric indices of nutritional status. The plasma maximal oxidation rate was significantly increased in cirrhotic patients (P <.01) and was inversely related to the serum concentration of vitamin E (P <.05). We conclude that lipoprotein alterations and not nutritional factors should be regarded as major factors explaining serum vitamin E reduction in patients with parenchymal liver cirrhosis, and that vitamin E depletion is associated with an increased plasma susceptibility to oxidation.

<Abst<em>r</em>actText>Retinol binding p<em>r</em>otein 4 (RBP4) ca<em>r</em><em>r</em>ies <em>r</em>etinol in plasma, but is also conside<em>r</em>ed an adipokine, as it is implicated in insulin <em>r</em>esistance in mice. Plasma RBP4 co<em>r</em><em>r</em>elates with total choleste<em>r</em>ol, low density lipop<em>r</em>otein (LDL)-choleste<em>r</em>ol and t<em>r</em>iglyce<em>r</em>ides, and may confe<em>r</em> inc<em>r</em>eased ca<em>r</em>diovascula<em>r</em> <em>r</em>isk. Howeve<em>r</em>, cont<em>r</em>ove<em>r</em>sy exists about ci<em>r</em>culating RPB4 levels in type 2 diabetes mellitus (T2DM) and obesity. He<em>r</em>e, we analyzed the <em>r</em>elationships of RBP4 and <em>r</em>etinol with lipop<em>r</em>otein subf<em>r</em>actions in subjects with and without T2DM.</Abst<em>r</em>actText><Abst<em>r</em>actText>Fasting plasma RBP4 (enzyme-linked immunoso<em>r</em>bent assay) and <em>r</em>etinol (high pe<em>r</em>fo<em>r</em>mance liquid ch<em>r</em>omatog<em>r</em>aphy) we<em>r</em>e assayed in 41 T2DM subjects and 37 non-diabetic subjects. Lipop<em>r</em>otein subf<em>r</em>actions (NMR spect<em>r</em>oscopy) we<em>r</em>e measu<em>r</em>ed in 36 T2DM subjects and 27 non-diabetic subjects. Physical inte<em>r</em>action of RBP4 with lipop<em>r</em>oteins was assessed by fast p<em>r</em>otein liquid ch<em>r</em>omatog<em>r</em>aphy (FPLC).</Abst<em>r</em>actText><p><div><b>RESULTS</b></div>Plasma RBP4 and <em>r</em>etinol we<em>r</em>e st<em>r</em>ongly co<em>r</em><em>r</em>elated (<em>r</em> = 0.881, <i>p</i> < 0.001). RBP4, <em>r</em>etinol and the RBP4/<em>r</em>etinol <em>r</em>atio we<em>r</em>e not diffe<em>r</em>ent between T2DM and non-diabetic subjects (all <i>p</i> > 0.12), and we<em>r</em>e un<em>r</em>elated to body mass index. Notably, RBP4 and <em>r</em>etinol we<em>r</em>e elevated in subjects with metabolic synd<em>r</em>ome (<i>p</i> < 0.05), which was att<em>r</em>ibutable to an association with elevated t<em>r</em>iglyce<em>r</em>ides (<i>p</i> = 0.013). La<em>r</em>ge <em>VLDL</em>, total LDL and small LDL we<em>r</em>e inc<em>r</em>eased in T2DM subjects (<i>p</i> = 0.035 to 0.003). Taking all subjects togethe<em>r</em>, RBP4 co<em>r</em><em>r</em>elated with total choleste<em>r</em>ol, non-HDL choleste<em>r</em>ol, LDL choleste<em>r</em>ol, t<em>r</em>iglyce<em>r</em>ides and apolipop<em>r</em>otein B in univa<em>r</em>iate analysis (<i>p</i> < 0.001 fo<em>r</em> each). Age-, sex- and diabetes status-adjusted multiva<em>r</em>iable linea<em>r</em> <em>r</em>eg<em>r</em>ession analysis <em>r</em>evealed that RBP4 was independently associated with la<em>r</em>ge <em>VLDL</em> (β = 0.444, <i>p</i> = 0.005) and small LDL pa<em>r</em>ticles (β = 0.539, <i>p</i> < 0.001). Its <em>r</em>elationship with la<em>r</em>ge <em>VLDL</em> <em>r</em>emained afte<em>r</em> fu<em>r</em>the<em>r</em> adjustment fo<em>r</em> <em>r</em>etinol. RBP4 did not co-elute with <em>VLDL</em> no<em>r</em> LDL pa<em>r</em>ticles in FPLC analyses.</p><Abst<em>r</em>actText>Plasma RBP4 levels a<em>r</em>e <em>r</em>elated to but do not physically inte<em>r</em>act with la<em>r</em>ge <em>VLDL</em> and small LDL pa<em>r</em>ticles. Elevated RBP4 may cont<em>r</em>ibute to a p<em>r</em>oathe<em>r</em>ogenic plasma lipop<em>r</em>otein p<em>r</em>ofile.</Abst<em>r</em>actText>

A lipolytic activity for beta-endorphin (beta EP) has been recently suggested both in vitro and in vivo. In our study we evaluated the relationship between beta EP and blood lipid pattern in Type 2 (non-insulin dependent) diabetic patients. Plasma beta EP, together with plasma beta-lipotropin (beta LPH), ACTH, cortisol and plasma insulin (IRI), was measured by RIA after silicic acid plasma extraction and Sephedex G-75 column chromatography. Although reduced beta EP (7.12 +/- 3.8 fmol/ml) and increased beta LPH (9.3 +/- 3.7 fmol/ml) levels were found in diabetic patients, compared to controls (8.53 +/- 3.3 fmol/ml, p less than 0.05 and 8.34 +/- 2.6 fmol/ml, p less than 0.05, respectively), higher plasma beta EP concentrations were demonstrated in hyperlipidemic diabetic patients (10.3 +/- 3.9 fmol/ml) than in patients with normal blood lipid pattern (4.85 +/- 1.45 fmol/ml, p less than 0.001). Several positive correlations between beta EP, plasma free fatty acids (r = 0.75, p less than 0.001), triglycerides (r = 0.84, p less than 0.001) and VLDL (r = 0.80, p less than 0.001) were found in our patients independently of overweight, hypoglycemic treatment, plasma IRI levels and of the degree of metabolic control. A higher prevalence of micro- and macrovascular complications was demonstrated in hyperlipidemic than in normolipidemic patients. Blood lipid disorders might therefore be associated with increased plasma beta EP levels in Type 2 diabetes.