Apolipoprotein-E phenotype and basal activity of low-density lipoprotein receptor are independent of changes in plasma lipoprotein subfractions after cholesterol ingestion in Japanese subjects

We investigated whether the apolipoprotein-E (apoE) phenotype and the basal activity of low-density lipoprotein (LDL) receptor, which were reported to be the major determinants for increase in plasma LDL levels by cholesterol ingestion, have the same role in Japanese subjects whose diet is low in fat and cholesterol. Cholesterol (750 mg/d) was added to the ordinary diet as a dried egg-yolk supplement for 4 wk to 110 subjects. Plasma levels of lipids, apolipoproteins, and cholesterol in lipoprotein subfractions were measured at the beginning and end of the test period. Phenotyping of apoE was determined by an isoelectric focusing-immunoblotting method, and LDL receptor activity in lymphocytes was determined by flow cytometry. Plasma levels of cholesterol in less-dense LDL (LDL(1)) and less-dense high-density lipoprotein (HDL(2)) were slightly but significantly increased, 3.4% and 4.1%, respectively, by cholesterol ingestion, but the increases were not statistically significant in any of E2, E3, and E4 groups. The distribution of the apoE phenotype was equivalent in all three LDL-cholesterol groups (no change, increase, and decrease by cholesterol ingestion). Plasma levels of LDL, LDL(1), and LDL(2) cholesterol were not significantly increased in the three groups of subjects with lymphocyte LDL-receptor activities (low, medium, and high). As with apoE phenotype, LDL-receptor activities were the same in all three LDL-cholesterol groups. In addition, there were no significant correlations between LDL-receptor activity and changes in plasma levels of lipids, apolipoproteins, and cholesterol in lipoprotein subfractions. Therefore, we concluded that cholesterol ingestion significantly increases plasma levels of less-dense LDL and HDL, but neither apoE phenotype nor basal LDL-receptor activity explain the variability in changes in plasma lipoprotein subfractions by cholesterol ingestion in Japanese subjects.     

Magnesium deficiency affects plasma lipoprotein composition in rats

Weanling rats were pair-fed for 8 d with control and Mg-deficient diets containing 960 and 30 mg of Mg/kg, respectively. The marked reduction in plasma Mg levels indicated that the rats fed the Mg-deficient diet were indeed deficient. In the Mg-deficient rats the percent composition of triglycerides in VLDL, LDL and HDL was elevated and that of protein was reduced. Although the proportion of cholesterol was reduced in LDL and HDL, that of phospholipid was decreased only in HDL. Magnesium deficiency induced a decrease in the percent composition of apolipoprotein (apo) E and a relative increase in the apo C for VLDL. In HDL from Mg-deficient rats, the proportion of apo AI was higher than normal, apo AIV was lower than normal and apo E was virtually absent. The percent composition of oleic and linoleic acids was increased but that of stearic and arachidonic acids was depressed in both VLDL and HDL derived from Mg-deficient rats compared with pair-fed controls. Whether these alterations in lipoprotein profile contribute to hyperlipoproteinemia or are the results of the metabolic changes that produce hyperlipoproteinemia remain to be determined.     

Effect of L-ascorbic acid on the oxidative modification of apolipoprotein E in human very-low-density lipoprotein

Antioxidant activity of L-ascorbic acid (AsA) against oxidative modification of apolipoprotein (apo) E in human very-low-density lipoprotein (VLDL) was investigated. The VLDL oxidation induced by peroxyl radicals and peroxynitrite led to lipid peroxidation and oxidative modification of apoE. The binding activity of apoE to heparin was decreased by the oxidative modification. AsA (200, 500, and 1,000 microm) inhibited both the lipid peroxidation and the oxidative modification of apoE. These results suggest that AsA prevents the biological function of apoE in VLDL from the oxidation by free radicals.     

Apolipoprotein E polymorphism and cardiovascular disease: a HuGE review

This review examines the association between the apolipoprotein (apo) var epsilon gene polymorphism (or its protein product (apo E)), metabolic regulation of cholesterol, and cardiovascular disease. The apo var epsilon gene is located at chromosome 19q13.2. Among the variants of this gene, alleles (*) epsilon2, (*) epsilon3, and (*) epsilon4 constitute the common polymorphism found in most populations. Of these variants, apo (*) epsilon3 is the most frequent (>60%) in all populations studied. The polymorphism has functional effects on lipoprotein metabolism mediated through the hepatic binding, uptake, and catabolism of chylomicrons, chylomicron remnants, very low density lipoprotein (VLDL), and high density lipoprotein subspecies. Apo E is the primary ligand for two receptors, the low density lipoprotein (LDL) receptor (also known as the B/E receptor) found on the liver and other tissues and an apo E-specific receptor found on the liver. The coordinate interaction of these lipoprotein complexes with their receptors forms the basis for the metabolic regulation of cholesterol. Allelic variation in apo var epsilon is consistently associated with plasma concentrations of total cholesterol, LDL cholesterol, and apo B (the major protein of LDL, VLDL, and chylomicrons). Apo var epsilon has been studied in disorders associated with elevated cholesterol levels or lipid derangements (i.e., hyperlipoproteinemia type III, coronary heart disease, strokes, peripheral artery disease, and diabetes mellitus). The apo var epsilon genotype yields poor predictive values when screening for clinically defined atherosclerosis despite positive, but modest associations with plaque and coronary heart disease outcomes. In addition to genotype-phenotype associations with vascular disease, the alleles and isoforms of apo var epsilon have been related to dementias, most commonly Alzheimer's disease.     

The inhibitory effect of soy protein isolate on atherosclerosis in mice does not require the presence of LDL receptors or alteration of plasma lipoproteins.

The mechanisms by which dietary soy favorably influences lipoprotein metabolism and inhibits atherosclerosis are uncertain. Studies of blood mononuclear cells and cultured hepatocytes have indicated that certain soy peptides (i.e., 7S globulins) stimulate expression of LDL receptors. This pathway represents a hypothetical mechanism by which soy's hypocholesterolemic and antiatherosclerotic effects may be mediated. However, direct evidence supporting this hypothesis is lacking. To address this, we compared effects of dietary soy protein isolate in two genetically engineered mouse models of atherosclerosis. One mouse [LDL receptor -/- + apolipoprotein (apo) B transgenic] is devoid of LDL receptors and overproduces apolipoprotein B, whereas the other (apoE -/-) has a normal complement of LDL receptors but does not produce apolipoprotein E. Male (n = 10-12/group) and ovariectomized female (n = 10-12/group) mice were studied. There were three treatment groups, which differed principally by the source of the protein component of the diet: 1) casein/lactalbumin (no isoflavones), 2) alcohol-washed soy protein isolate (total isoflavones = 0.04 mg/g), and 3) intact soy protein isolate (total isoflavones = 1.72 mg/g). Atherosclerosis was assessed by quantifying the aortic content of esterified cholesterol. Atherosclerosis was inhibited (relative to the casein/lactalbumin group) by both alcohol-washed (45 and 31%) (P < 0.05) and intact (65 and 41%) (P < 0.05) soy protein isolate in LDL receptor -/- and apoE -/- mice, respectively. There was no sex difference. In a two-way analysis, there were significant effects of type of soy isolate and type of mouse. The antiatherosclerosis effect was enhanced in LDL receptor -/- mice (P < 0.001) and diminished in mice fed alcohol-washed soy protein isolate (P < 0.001). Furthermore, inhibitory effects of soy on atherosclerosis were unrelated to plasma LDL, VLDL or HDL cholesterol concentrations. The results represent direct evidence for the existence of LDL receptor- and plasma lipoprotein-independent pathways by which dietary soy protein isolate inhibits atherosclerosis.     

The effect of dietary fat saturation on plasma and hepatic lipoproteins in the rat

Semipurified diets containing 10% kilocalories from either safflower oil (SO), corn oil (CO), olive oil (OO) or palm oil (PO) were fed to weanling male rats for 2 weeks. The effects of dietary fat saturation on plasma lipids and lipoproteins were: 1) Nonfasted plasma cholesterol concentration was higher in rats fed OO (mean +/- SEM = 81.0 +/- 2.9 mg/dl) vs. CO (67.5 +/- 2.9); 2) plasma chylomicron cholesterol concentration was higher in rats fed OO vs. SO and CO, with PO values in between; and 3) the cholesterol concentration of plasma very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) did not differ among groups. The effects of dietary fat saturation on hepatic lipoproteins (determined by liver perfusion techniques) were: 1) hepatic higher density lipoprotein (d = 1.006-1.21 g/ml) cholesterol production was greater in rats fed SO and CO vs. PO [19.1 +/- 1.2, 17.2 +/- 0.8 and 13.7 +/- 1.6 micrograms/(g liver X 1.5 hour), respectively]; 2) there was no difference in hepatic VLDL cholesterol production among groups; and 3) the ratio of cholesterol to protein of hepatic VLDL and the higher density lipoprotein fraction was higher in rats fed diets rich in polyunsaturated fatty acids versus saturated fatty acids. Dietary fat saturation had no effect on carcass and liver cholesterol concentrations. Since differences in hepatic lipoprotein production were not reflected in plasma lipoprotein patterns, these results suggest that extrahepatic lipoprotein metabolism differs in rats fed diets containing fatty acids of varying saturation.     

Distribution of circulating beta-carotene in human plasma lipoproteins.

We examined the distribution of beta-carotene in plasma lipoprotein fractions. In healthy children and adults, LDL contained more beta-carotene than did HDL, but in cord blood more beta-carotene was found in HDL than in LDL. After the oral administration of beta-carotene, its plasma level rose although its distribution in the individual lipoprotein fractions did not change. Among disease conditions associated with hyperlipidemia, the ratio of beta-carotene to plasma lipids was highest in anorexia nervosa, while nephrotic syndrome and diabetes mellitus had similar ratios to each other.     

Investigating Effects of Plasma Apolipoprotein E on Ischemic Heart Disease Using Mendelian Randomization Study

Background: Observationally plasma apolipoprotein E (apoE) is positively associated with ischemic heart disease (IHD). A Mendelian randomization (MR) study suggesting apoE is unrelated to cardiovascular mortality did not consider specific isoforms. We used MR to obtain estimates of plasma apoE2, apoE3 and apoE4 on IHD, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, triglycerides and apolipoprotein B (apoB). Methods: We obtained independent genetic instruments from proteome genome-wide association studies (GWAS) and applied them to large outcome GWAS. We used univariable MR to assess the role of each isoform and multivariable MR to assess direct effects. Results: In univariable MR, apoE4 was positively associated with IHD (odds ratio (OR) 1.05, 95% confidence interval (CI) 1.01 to 1.09), but apoE2 and apoE3 were less clearly associated. Using multivariable MR an association of apoE2 with IHD (OR 1.16, 95% CI 0.98 to 1.38) could not be excluded, and associations of apoE3 and apoE4 with IHD were not obvious. In univariable MR, apoE2 and apoE4 were positively associated with apoB, and a positive association of apoE2 with LDL cholesterol could not be excluded. Using multivariable MR apoE2 was positively associated with LDL cholesterol, and associations with apoB could not be excluded. After adjusting for apoB, no direct effects of apoE isoforms on IHD were evident. Conclusions: Plasma apoE2 and apoE4 may play a role in lipid modulation and IHD. Whether apoE could be a potential therapeutic target requires further clarification when larger genetic studies of apoE isoforms are available.     

Effect of beta-carotene supplementation on the concentrations and distribution of carotenoids,vitamin E,vitamin A,and cholesterol in plasma lipoprotein and non-lipoprotein fractions in healthy older women.

We studied the effect of beta-carotene supplementation on the concentrations and distribution in plasma lipoprotein and non-lipoprotein fractions of carotenoids, alpha-tocopherol, retinol, and cholesterol.

Ten women ingested either 90 mg of beta-carotene or placebo daily for 3 weeks while residing in their homes and eating their usual meals. Carotenoids (beta-carotene, lycopene, lutein/zeaxanthin), retinol, alpha-tocopherol, and cholesterol were measured in plasma lipoprotein and non-lipoprotein fractions before and after treatment.

In the beta-carotene-supplemented group, total plasma beta-carotene increased 14-fold from 0.48 +/? 0.13 to 6.83 +/? 2.12 mumol/L (p = 0.04). Although the greatest increase in beta-carotene was in low-density-lipoproteins (LDL), the magnitude of increase was similar in LDL, high-density-lipoproteins (HDL), and very-low-density-lipoproteins (VLDL). Thus, the relative distribution of beta-carotene in lipoproteins was unchanged: approximately 71% was in LDL, approximately 15% in HDL and approximately 12% in VLDL, before and after beta-carotene supplementation. There were no changes in amounts and distribution in lipoproteins of the other carotenoids, alpha-tocopherol, and cholesterol. There was no change in the amount of retinol in lipoprotein-deficient plasma. There were no changes in total plasma triglycerides. Significant positive correlations were found between LDL- or VLDL-cholesterol and alpha-tocopherol in LDL or VLDL, respectively; between LDL- or VLDL-cholesterol and lutein/zeaxanthin in LDL or VLDL, respectively; and between HDL-cholesterol and beta-carotene in HDL.

beta-Carotene supplementation (90 mg/day for 3 weeks) in healthy older women results in an enrichment of all plasma lipoprotein fractions with beta-carotene, but does not alter the relative distribution of beta-carotene in lipoproteins. beta-Carotene supplementation has no effect on the amounts and relative distribution of lycopene, lutein/zeaxanthin, and alpha-tocopherol in lipoproteins, or of retinol in the non-lipoprotein fraction of plasma. Short-term beta-carotene supplementation has no effect on the concentrations of plasma total triglycerides, total cholesterol, HDL-, LDL-, and VLDL-cholesterol.     

The effect of milk and skim milk intake on serum lipids and apoproteins in young females

The effect of milk and skim milk intake on serum lipid and apoprotein levels was investigated in young females with consideration of each subject's menstrual period. When milk and dairy products were not allowed, the serum cholesterol concentration tended to decrease in high density lipoprotein (HDL) and very low density lipoprotein (VLDL), the triglyceride concentration tended to increase in HDL and low density lipoprotein (LDL), the phospholipid concentration showed no change, and the apoB, apoC-III and apoE significantly decreased. In the milk group, VLDL cholesterol and phospholipid concentrations were increased with a significant increase in the apoB concentration after intake of 200 ml/day of milk for one menstrual period, and these levels did not change when the milk intake was doubled. VLDL phospholipid increased and apoE decreased after the intake of 20 g/day of skim milk, and LDL cholesterol and HDL phospholipid concentrations tended to decrease when the skim milk intake was doubled.     

ApoE distribution among lipoproteins of rhesus monkeys is modulated by dietary fat and cholesterol

The effect of dietary saturated fat and cholesterol on plasma cholesterol and apolipoprotein E (apoE) distribution among lipoproteins was studied in rhesus monkeys. Two groups of four monkeys had been fed diets containing 31% energy as either corn oil or coconut oil for 5 yr from birth. Each group was then fed short-term their respective diet with a 0.2% cholesterol supplement, the opposite fat without cholesterol, the opposite fat +0.2% cholesterol, followed by their original fat without cholesterol for 5 to 8 wk periods. Plasma was assayed for total cholesterol, total triglyclerides, and the distribution of apoE within lipoproteins (VLDL, IDL, LDL, HDL) separated by gradient-density electrophoresis. When coconut oil was fed, plasma cholesterol and triglyceride concentrations were 134% and 157%, respectively, of the levels when corn oil was fed. Cholesterol supplementation of corn oil also elevated the plasma cholesterol (141%), whereas cholesterol supplementation of coconut oil appeared to induce a synergistic increase (198%). Both groups of monkeys responded similarly to a given diet. The distribution of apoE in lipoproteins differed according to dietary treatment, with cholesterol feeding causing a major shift from HDL to IDL, whereas coconut oil caused a modest shift from HDL to VLDL. The relative amount of apoE in LDL was unchanged by diet. We conclude that dietary saturated fat or cholesterol can modulate the apoE distribution within lipoproteins in rhesus monkeys in conjunction with the previously noted expansion of the cholesteryl ester pool in VLDL and IDL.     

Dietary restriction amplifies the hypercholesterolemic effect of cholesterol feeding in the rat

Dietary restriction (half of the control ration) was performed in rats given either standard or hypercholesterolemic diets. The plasma cholesterol was measured throughout the 2 month experiment after which time the lipoproteins were analysed. Underfed rats with or without cholesterol supplementation showed a rapid rise in plasma cholesterol. Moreover, dietary restriction greatly enhanced the effect of the hypercholesterolemic diet which contained cholesterol and cholic acid. The major changes occurred in the very low density lipoprotein (VLDL) cholesterol which was increased in cholesterol-fed rats. This was amplified more than 2-fold by dietary restriction. In addition cholesterol feeding associated with dietary restriction induced a significant rise in the intermediate density lipoprotein (IDL)+low density lipoprotein (LDL) cholesterol. The findings indicate that dietary restriction could be an additional risk factor of hyperlipoproteinemia, specially when associated with high cholesterol intake.     

Elevated plasma lipids in patients with binge eating disorders are found only in those who are anorexic

OBJECTIVE: We have previously shown that patients with restricting type anorexia nervosa (AN-R) have low plasma lipid levels, which increase with refeeding. In this study, we investigated plasma lipid levels in patients with eating disorders, distinguishing between individuals with bulimia nervosa (BN) and anorexia nervosa of the binge eating/purging type (AN-B). METHODS: We examined the fasting lipid levels in individuals with BN (n = 10) and AN-B (n = 9), and compared these findings with a group of age-matched normal weight healthy controls (C) (n = 10). RESULTS: The AN-B group had significantly higher concentrations of total plasma cholesterol, apolipoprotein (apo) B, apoA1, and low-density lipoprotein (LDL)-cholesterol than both control and BN groups (p < .05). The AN-B group also had higher plasma triglycerides and intermediate-density lipoprotein (IDL)-apo B levels (p < .05) than controls. DISCUSSION: In conclusion, the issue of hyperlipidemia in patients with eating disorders is a complex one and this study, taken together with the findings of our previous study, demonstrates the importance of carefully distinguishing between the major types of eating disorders (AN-R, BN, and AN-B) when examining plasma lipid levels.     

Lipidemic effects of a mild-term treatment with calcium heparin in vasculopathic subjects

The Authors study the lipidemic effects of a "middle-term" treatment with heparin calcium in vasculopathic subjects undergoing the drug for antithrombotic purposes. The series consists of 35 subjects (21 m, 14 f, mean age 57 +/- 8) suffering from peripheral arteriopathy (24 cases) and instable angina (11 cases) of arteriosclerotic nature, and free from endocrinometabolic and hepatorenal diseases; all the subjects were normolipemic, except for 4 cases having hyperlipoproteinemia of type II B. After a week of standard diet and drug wash-out, each patient underwent antithrombotic treatment with calcium heparin (10.000 Units subcutaneously) for three weeks during the hospitalization; for each sample, the plasma levels of triglycerides (TG), total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), HDL-3-cholesterol (HDL-3-C) and HDL-2-cholesterol (HDL-2-C) were determined enzymatically (kits Boerhinger Mannheim). The Authors observe a significant (P less than 0.05) increase of TC and LDL-C after one and after two weeks of treatment with a return to the baseline after three weeks; levels of TG, HDL-C, HDL-3-C, HDL-2-C and the HDL-C/TC and HDL-2-C/HDL-C ratios showed an ascending profile until the third week without significant changes, compared to the baseline values. Subdividing the series arbitrarily into into two groups (A and B) respectively having rather low ("normolipemic") and high ("hyperlipemic") values of TC and TG respectively below (group A) and above (group B) 230 mg/dl (TC) and 165 mg/dl (TG).(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum beta-carotene in anorexia nervosa patients: a case-control study.

OBJECTIVE: To study the prevalence of hypercarotenemia in a large cohort of patients with anorexia nervosa (AN), to compare serum beta-carotene (betaC) values among restricting and purging AN subjects, and to investigate whether hypercarotenemia is related to an increase in low-density lipoprotein (LDL) cholesterol. METHOD: Retrospective case-control study including 101 female patients and 95 age-matched normal controls in whom fasting serum betaC and lipid profiles were determined. RESULTS: The prevalence of hypercarotenemia (>200 microg/dl) in the AN population was 62%. Mean serum betaC level was significantly higher in AN patients than in controls (237 +/- 103 vs. 160 +/- 45 microg/dl, p <.0001). Among AN patients, the level was higher in restricters than in purgers (271 +/- 110 vs. 186 +/- 78 microg/dl, p <.005). Fasting serum total and LDL cholesterol levels were also significantly higher in patients with AN than in controls, but no correlation was found between serum betaC and LDL cholesterol values. DISCUSSION: Hypercarotenemia is a common finding in AN patients, especially in the restricter subgroup. The high prevalence of elevated serum betaC in AN patients supports its diagnostic value in atypical forms of eating disorders.     

Vegetable oils affect the composition of lipoproteins in sea bream (Sparus aurata)

The aim of the present study was to determine the influence of the dietary fatty acid profile on the lipoprotein composition in sea bream fed different vegetable oils. Six experimental diets were formulated combining fish oil with three vegetable oils (soybean, rapeseed, linseed) in order to obtain 60-80 % (w/w) fish-oil replacement. VLDL, LDL and HDL in plasma samples were obtained by sequential centrifugal flotation. The lipid class, protein content and fatty acid composition of each lipoprotein fraction were analysed. HDL was the predominant lipoprotein in sea bream plasma containing the highest proportion of protein (34 %) and phosphatidylcholine. LDL presented a high content of cholesterol, whereas triacylglycerol comprised a larger proportion of VLDL. The lipid class of the lipoprotein fractions was affected by the dietary vegetable oils. Thus, a high dietary inclusion of soyabean and linseed oil (80 %) increased the cholesterol in HDL and LDL in comparison to fish oil. Similarly, the triacylglycerol concentration of VLDL was increased in fish fed 80 % soyabean and linseed oils owing to the low n-3 highly unsaturated fatty acid content of these diets. Lipoprotein fatty acid composition easily responded to dietary fatty acid composition. VLDL was the fraction more affected by dietary fatty acid, followed by LDL and HDL. The n-3 highly unsaturated fatty acid content increased in the order VLDL less than LDL and less than HDL, regardless of dietary vegetable oils.     

Fish oil attenuates the cholesterol induced rise in lipoprotein cholesterol

Fish oils rich in n-3 fatty acids lower plasma triglyceride profoundly but the effect on plasma cholesterol is not clear. This study tested the capacity of MaxEPA oil to modify the rise in lipoprotein cholesterol during cholesterol-rich diets. Six subjects were tested with three diets: 1) habitual (P/S 0.47, cholesterol 710 mg/d); 2) fish oil (40 g/d MaxEPA, P/S 1.62, cholesterol 190 mg/d); 3) fish oil + egg yolk (P/S 1.62, cholesterol 940 mg/d). Changing from habitual to fish oil significantly lowered cholesterol and triglyceride levels in plasma, VLDL, LDL, and HDL and in plasma apo-A1 and apo-B. However the addition of 750 mg/d cholesterol to the fish oil failed to raise lipoprotein cholesterol or apoprotein levels significantly, although plasma cholesterol rose slightly; n-3 fatty acids are therefore capable of lowering lipoprotein cholesterol even when the intake of cholesterol is high.     

Lipoproteins and liver lipids in copper-deficient rats

The influence of dietary copper deficiency on plasma lipoproteins and liver lipids was examined in rats using cholesterol free, semi-purified diets in two separate experiments. In Experiment 1, copper deficiency was associated with a 91% elevation in plasma cholesterol and a 13% decrease in HDL cholesterol. The normal HDL/(VLDL+LDL) cholesterol ratio of 2:1 in copper-adequate rats was essentially reversed by copper deficiency. Aortic cholesterol concentration was increased by 15% in copper-deficient rats. In Experiment 2 copper deficiency produced very similar changes in plasma lipoproteins as observed in Experiment 1. In addition, copper deficiency was associated with an increase in HDL free cholesterol, a decrease in HDL cholesteryl esters, a marked increase in (VLDL+LDL) cholesteryl esters with a smaller increase in free cholesterol of (VLDL+LDL). Copper deficiency was associated with a decrease in liver cholesteryl ester concentrations, but no changes in liver free cholesterol. Liver triglycerides were also decreased by copper deficiency and plasma triglycerides were markedly increased. Possible effects of dietary copper deficiency on lipoprotein and cholesterol metabolism are discussed.     

脂蛋白在脂多糖诱导THP-1细胞活化中的调节机制

目的 研究血清脂蛋白对脂多糖的影响机制,并对不同种类脂蛋白:高密度脂蛋白(HDL)、低密度脂蛋白(LDL)和极低密度脂蛋白(VLDL),抑制脂多糖的能力进行比较,为研究脂蛋白在治疗败血症中的应用提供理论基础.方法 通过检测经佛波醇酯刺激分化的THP-1细胞分泌的TNF-α间接反映脂蛋白对脂多糖的抑制作用.将不同浓度脂多糖与THP-1细胞在血清基质中混合孵育4 h,并与3种脂蛋白-脂多糖混合液与THP-1细胞混合孵育后TNF-α的分泌量进行对比,计算脂蛋白对脂多糖的抑制情况.结果 HDL、LDL和VLDL单独不能诱导分化的THP-1细胞分泌TNF-α(P＞0.05).当10 ng/mL脂多糖与0.05 mg/m以上浓度的脂蛋白(HDL、LDL和VLDL)混合时,TNF-α分泌量明显降低.当脂多糖浓度为100 ng/mL时,0.1 mg/mL的脂蛋白(HDL、LDL和VLDL)对其抑制效果较低,分别为(20.7±11.1)%、(8.9±2.8)%、(4.3±1.6)%;在脂多糖浓度为10 ng/mL抑制效果明显增强,抑制率分别为(69.3±3.7)%、(42.9±5.7)%、(42.7±4.5)%.HDL对各浓度脂多糖的抑制效果均强于LDL和VLDL(P＜0.05).结论 脂蛋白在血清中能抑制脂多糖活化巨噬细胞分泌细胞因子,但抑制效果在脂多糖浓度高时相比浓度低时差.HDL对脂多糖活化巨噬细胞的抑制作用比LDL和VLDL强.     

Soluble oat fiber tends to normalize lipoprotein composition in cholesterol-fed rats

The effect of oat fiber on VLDL, LDL and HDL composition was investigated by feeding male Sprague-Dawley rats diets containing 1.0% cholesterol and 0.2% cholic acid, and 6% dietary fiber from oat bran, high-fiber oat flour or a processed oat product for 20 d. Compared to cholesterol-fed cellulose controls, all oat fibers altered the response to cholesterol feeding as indicated by 25-45% lower total lipoprotein cholesterol, 40-60% lower VLDL + LDL cholesterol, and 25-40% higher HDL cholesterol contents, P less than 0.01. The effect of the oat fibers on VLDL composition was especially pronounced as demonstrated by 30-65% lower VLDL protein, VLDL apo E and plasma apo B concentrations. The processed oat product which contained 40% more soluble fiber than oat bran or oat flour normalized the lipoprotein profile associated with ingestion of the atherogenic diet significantly more than oat bran or oat flour. Concentration of total lipoprotein cholesterol and distribution of apo E among the VLDL and LDL fractions in the processed oat product group were similar to controls not fed cholesterol. These data indicate that ingestion of oat fiber tends to normalize the lipoprotein profile induced by feeding an atherogenic diet in the rat, and that the hypocholesterolemic effect of oat fiber is associated with its soluble fiber content.