燕麦膳食纤维对肠道胆固醇吸收的影响及机制研究

  目的  探讨燕麦纤维对脂代谢紊乱小鼠肠道胆固醇代谢的影响及其机制。  方法  选用6周龄雄性C57BL/6小鼠36只,按体重随机分为3组：阴性对照组、模型对照组和燕麦纤维组,预防性干预24周。实验结束后,检测血清甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）、空腹血糖和胰岛素水平以及肝组织中TG和TC水平。Western blot法测定小肠组织中肝X受体 α（LXRα）、三磷酸腺苷结合盒转运子A1（ABCA1）和G1（ABCG1）蛋白的表达水平。  结果  干预24周后,与模型对照组比较,燕麦纤维组小鼠血清TC、LDL-C水平[分别为（2.02 ± 0.44）、（0.54 ± 0.27）mmol/L]降低,HDL-C水平[（1.05 ± 0.19）mmol/L]升高（P < 0.05）;燕麦纤维组小鼠空腹血糖[（6.68 ± 1.32）mmol/L）和胰岛素抵抗指数（3.66 ± 1.28）明显下降;燕麦纤维组小鼠小肠上段组织中LXRα、ABCA1、ABCG1蛋白表达量[分别为（0.68 ± 0.14）、（0.96 ± 0.24）、（0.59 ± 0.15）]均明显升高（P < 0.05）。  结论  燕麦纤维可降低脂代谢紊乱小鼠血脂水平,增加肠道胆固醇外流;其机制可能与燕麦纤维上调小肠组织中LXRα、ABCA1和ABCG1的蛋白表达有关。     

ABCA1和ABCG1在胆固醇逆转运中作用的研究进展

胆固醇逆转运是机体排除过多胆固醇的唯一途径,对维持生物体胆固醇代谢稳态有着重大意义。ATP结合盒转运体A1（ABCA1）和ATP结合盒转运体G1（ABCG1）是ATP结合盒转运体家族中的一员,它们通过不同的机制在胆固醇逆转运中起着重要作用。关于ABCA1和ABCG1研究很多,而对于两者在胆固醇逆转运中的联合作用的文献较少。本文就国外ABCA1和ABCG1在胆固醇逆转运中的研究进展进行综述。     

Correlation between the cholesterolemic responses produced by dietary cholesterol and casein in rabbits

Rabbits were fed three semipurified diets, namely a cholesterol-free soy protein diet, a cholesterol-free casein diet or a diet containing soy protein plus cholesterol (2 g/kg). One group (Chol-Cas) of 24 rabbits was fed successively the diet containing soy protein plus cholesterol (25 days), the soy protein diet (36 days) and the casein diet (20 days). Another group (Cas-Chol) consisting of 25 animals received consecutively the diet containing casein, soy protein and soy protein supplemented with cholesterol. Hypercholesterolemia was induced by the diets containing cholesterol or casein, whereas regression was seen on the soy protein diet. Within the Chol-Cas or Cas-Chol group the cholesterolemic response to casein and that to cholesterol was significantly correlated, the correlation coefficient being as high as 0.66. This correlation was still observed when calculated for animals either hypo- or hyperresponsive to dietary casein or cholesterol. When all animals were pooled, the correlation coefficient for the cholesterolemic response to casein and to cholesterol was only 0.33. The mean response to dietary cholesterol and to casein was significantly higher in the last dietary period than in the first period.     

The research progression of ABCA1 and ABCG1 in reverse cholesterol transport

胆固醇逆转运是机体排除过多胆固醇的唯一途径,对维持生物体胆固醇代谢稳态有着重大意义.ATP结合盒转运体A1(ABCA1)和ATP结合盒转运体G1(ABCG1)是ATP结合盒转运体家族中的一员,它们通过不同的机制在胆固醇逆转运中起着重要作用.关于ABCA1和ABCG1研究很多,而对于两者在胆固醇逆转运中的联合作用的文献较少.本文就国外ABCA1和ABCG1在胆固醇逆转运中的研究进展进行综述.     

Serum lipid and lipoprotein responses of six nonhuman primate species to dietary changes in cholesterol levels.

The response of serum lipids and lipoproteins to different levels of cholesterol in the diet was studied in chimpanzee (Pan troglodytes), rhesus (Macaca mulatta), green (Cercopithecus aethiops), patas (Erythrocebus patas), squirrel (Saimiri sciurea) and spider (Ateles sp.) monkeys. Five animals of each species were fed increasing amounts of dietary cholesterol (0.05% to 1.5% W/W) for 3-week periods; between each experimental diet, the animals were fed a basal diet without cholesterol for a similar period. Serum cholesterol response of different species measured in terms of response index (area under the time-concentration curve above basal value) varied with the dietary cholesterol content and showed a significant interspecies difference at 0.5% dietary cholesterol (1.8 mg/kcal) level. The overall response for the different diets allowed ranking of the species as follows: squirrel greater than green greater than spider approximately equal to rhesus approximately equal to patas greater than chimpanzee. The serum lipoprotein response was reflected not only in an increase in beta-lipoprotein but also in alpha-liprotein with significant differences among species in the amount of cholesterol transported in the lipoprotein classes. Challenging the animals with dietary cholesterol seems to be an essential step for determining inter- and intraspecies differences.     

胆固醇酯转运蛋白基因多态性与肥胖及对膳食干预的影响

目的探讨胆固醇酯转运蛋白(CETP)基因多态性与肥胖的关系及其对肥胖膳食干预的影响。方法从血凝块中提取DNA,用聚合酶链反应和限制性片段长度多态性方法(PCR-RFLP)检测上海340名成年人的CETP基因TaqIB位点多态性;对研究对象进行体格检查并测定血脂;对其中的肥胖人群进行膳食干预,分析CETP基因多态性对干预效果的影响。结果(1)B1B1、B1B2和B2B2三种基因型的频率分别为35·6%、47·9%和16·5%,符合Hardy-Weinberg定律;B1等位基因为优势等位基因;肥胖组人群和正常组的基因型构成差异无显著性,控制相关影响因素后结果相同。(2)三种基因型的高密度脂蛋白(HDL)水平差异有显著性,B2B2型的HDL水平最高。控制环境影响因素后这种相关性仍然存在。(3)B1B2型膳食干预后HDL水平明显升高,这与其他基因型显著不同;控制基线HDL水平和性别因素后基因型对HDL水平改变没有影响。结论CETP-TaqIB位点B2B2基因型具有较高的血清HDL水平,成年肥胖人中此位点多态性无特殊性;基线HDL水平影响不同基因型的HDL对膳食干预的反应。     

Association of gene polymorphism at cholesterol ester transfer protein locus with obesity and response to dietary intervention in obesity]

OBJECTIVE: To study the association of gene polymorphism at cholesterol ester transfer protein (CETP) locus with obesity and response to dietary intervention in obesity. METHODS: The PCR-PFLP method was used to detect the polymorphism of CETP gene of 340 adults in Shanghai. The levels of serum lipid profile, including TG, TC, HDL and LDL were analyzed. Obesity was selected to dietary intervention. RESULTS: (1)The genotype frequencies of CETP-TaqIB B1 B1, B1 B2 and B2 B2 were 35.6%, 47.9% and 16.5% respectively, which were in agreement with Hardy-Weinberg equilibrium. There was no significant difference in the distribution of genotypes between the obesity group and control group. The result was same after several influence factors controlled. (2) The levels of HDL were significantly different among genotype groups. Subjects for the B2 B2 genotype had the highest HDL levels. The relationship was steady after adjusting several influence factors. (3)Subjects for the B1 B2 genotype had higher HDL level after intervention, which was significantly different to other genotype groups. After adjusting baseline HDL level and gender, genotype didn't effect the change in HDL. CONCLUSION: CETP-TaqIB gene polymorphism influenced serum HDL level. But this gene polymorphism at CETP locus wasn't especial in adult obesity. Baseline HDL level influenced the change in HDL response to dietary intervention in three genotype groups.     

Composition of and cholesterol in Araucana and commercial eggs

Araucana eggs from six sources and commercial-type white eggs of two major supermarket brands and from the University of California flock were collected and analyzed for cholesterol content of the yolk. The yolks of Araucana eggs were significantly higher in cholesterol than those of commercial white eggs.     

Characteristics of human hypo- and hyperresponders to dietary cholesterol

The characteristics of people whose serum cholesterol level is unusually susceptible to consumption of cholesterol were investigated. Thirty-two volunteers from the general population of Wageningen, the Netherlands, each participated in three controlled dietary trials in 1982. A low-cholesterol diet was fed during the first half and a high-cholesterol diet during the second half of each trial, and the change (response) of serum cholesterol was measured. The responses in the three trials were averaged to give each subject's mean responsiveness. Fecal excretion of cholesterol and its metabolites were measured in the second trial, and body cholesterol synthesis was calculated. Responsiveness showed a positive correlation with serum high density lipoprotein2 (HDL2) cholesterol (r = 0.41, p less than 0.05) and with serum total cholesterol level on a high-cholesterol diet (r = 0.31, p = 0.09). A negative relation was found with habitual cholesterol consumption (r = -0.62, p less than 0.01), with body mass index (r = -0.50, p less than 0.01), and with the rate of endogenous cholesterol synthesis (r = -0.40, p less than 0.05), but not with the reaction of endogenous cholesterol synthesis rate to an increased intake of cholesterol. No relation was found with age, sex, total caloric needs, or the ratio of primary to secondary fecal steroids. Upon multiple regression analysis, only habitual cholesterol intake and serum total and HDL2 cholesterol levels contributed significantly to the explanation of variance in responsiveness. Thus, a low habitual cholesterol intake, a high serum HDL2 cholesterol level, or a low body weight do not make one less susceptible to dietary cholesterol-induced hypercholesterolemia.     

Dietary cholesterol from eggs increases the ratio of total cholesterol to high-density lipoprotein cholesterol in humans: a meta-analysis

BACKGROUND: Several epidemiologic studies found no effect of egg consumption on the risk of coronary heart disease. It is possible that the adverse effect of eggs on LDL-cholesterol is offset by their favorable effect on HDL cholesterol. OBJECTIVE: The objective was to review the effect of dietary cholesterol on the ratio of total to HDL cholesterol. DESIGN: Studies were identified by MEDLINE and Biological Abstracts searches (from 1974 to June 1999) and by reviewing reference lists. In addition, we included data from a more recently published study. Studies were included if they had a crossover or parallel design with a control group, if the experimental diets differed only in the amount of dietary cholesterol or number of eggs and were fed for > or =14 d, and if HDL-cholesterol concentrations were reported. Of the 222 studies identified, 17 studies involving 556 subjects met these criteria. RESULTS: The addition of 100 mg dietary cholesterol/d increased the ratio of total to HDL cholesterol by 0.020 units (95% CI: 0.010, 0.030), total cholesterol concentrations by 0.056 mmol/L (2.2 mg/dL) (95% CI: 0.046, 0.065 mmol/L; 1.8, 2.5 mg/dL), and HDL-cholesterol concentrations by 0.008 mmol/L (0.3 mg/dL) (95% CI: 0.005, 0.010 mmol/L; 0.2, 0.4 mg/dL). CONCLUSIONS: Dietary cholesterol raises the ratio of total to HDL cholesterol and, therefore, adversely affects the cholesterol profile. The advice to limit cholesterol intake by reducing consumption of eggs and other cholesterol-rich foods may therefore still be valid.     

The importance of dietary cholesterol in coronary heart disease

Dietary cholesterol is important in the pathogenesis of atherosclerosis because of its strong influence in increasing the concentrations of plasma cholesterol and low-density lipoprotein (LDL). The cause and effect relationship of dietary cholesterol to atherosclerosis and plasma lipoproteins has been best demonstrated in the rhesus monkey: when fed dietary cholesterol, hypercholesterolemia, increased LDL, and later atherosclerosis and even myocardial infarction result. Significant regression of coronary atherosclerosis occurred when cholesterol was removed from the diet. Epidemiological observations throughout the world indicate a positive relationship between the amounts of dietary cholesterol and the mortality from coronary heart disease (CHD). In human beings, several dozen experiments show the strong influence of dietary cholesterol in increasing plasma cholesterol levels when the background diet is low in dietary cholesterol. The invariable result of dietary cholesterol feeding is an elevation of plasma cholesterol and LDL levels which occurs in normal subjects, in Tarahumara Indians, and in pregnant women, as well as in patients with a variety of hyperlipidemias. Even in outpatient studies conducted as a double-blind trial, dietary cholesterol had a hypercholesterolemic effect. However, in poorly controlled outpatient studies such effects have not always been demonstrated. Threshold and ceiling amounts for dietary cholesterol clearly exist for both animals and human beings. The threshold is that amount of dietary cholesterol which affects plasma cholesterol levels. As the quantity of cholesterol in the diet is gradually increased, the plasma cholesterol continues to rise until an apparent saturation point is reached. Thus, if one adds further large quantities of dietary cholesterol to an already cholesterol-rich diet, no further increase in plasma cholesterol concentrations will occur, because the ceiling has been exceeded. The “ceiling” explains why some experiments of dietary cholesterol feeding are negative.     

Existence of consistent hypo- and hyperresponders to dietary cholesterol in man

Hyper- and hyporesponsiveness of serum cholesterol to dietary cholesterol is an established concept in animals but not in man. The authors studied the stability of the individual response of serum cholesterol to dietary cholesterol in three controlled experiments in 1982. The subjects were volunteers from the general population living in or near Wageningen, the Netherlands. Each experiment had a low-cholesterol baseline period (121, 106, and 129 mg/day in experiments 1, 2, and 3, respectively) and a high-cholesterol test period (625, 673, and 989 mg/day). Duplicate portion analysis showed that dietary cholesterol was the only variable. The 94 healthy men and women who completed experiment 1 showed an increase (mean +/- standard deviation (SD] in serum cholesterol of 0.50 +/- 0.39 mmol/liter (19 +/- 15 mg/dl). Seventeen putative hyperresponders, defined by their response in experiment 1, were retested in experiments 2 and 3; they showed responses of 0.28 +/- 0.38 mmol/liter (11 +/- 15 mg/dl) and 0.82 +/- 0.35 mmol/liter (32 +/- 14 mg/dl), respectively. Fifteen hyporesponders, selected in experiment 1, showed responses in experiments 2 and 3 of 0.06 +/- 0.35 mmol/liter (2 +/- 14 mg/dl) and 0.47 +/- 0.26 mmol/liter (18 +/- 10 mg/dl), significantly lower than the corresponding values for hyperresponders. The standardized regression coefficient for individual responses in experiment 2 on those in experiment 1 was beta = 0.34 (p = 0.03, n = 32); the corresponding regression coefficient for experiment 3 and experiment 1 was 0.53 (p less than 0.01). After correction for intraindividual fluctuations the true responsiveness distribution was found to have a between-subject standard deviation of about 0.29 mmol/liter (11 mg/dl). This implies that if the mean response to a certain dietary cholesterol load amounts to e.g., 0.58 mmol/liter (22 mg/dl), then the 16% of subjects least susceptible to diet will experience a rise of only 0.29 mmol/liter (11 mg/dl) or less, while in the 16% of subjects most susceptible to diet, serum cholesterol will rise by 0.87 mmol/liter (34 mg/dl) or more. The authors conclude that modest differences in responsiveness of serum cholesterol to dietary cholesterol do exist in man, and that the wide scatter of responses observed in single experiments is largely due to chance fluctuations.     

A survey of serum and dietary carotenoids in captive wild animals

Accumulation of carotenoids varies greatly among animal species and is not fully characterized. Circulating carotenoid concentration data in captive wild animals are limited and may be useful for their management. Serum carotenoid concentrations and dietary intakes were surveyed and the extent of accumulation categorized for 76 species of captive wild animals at Brookfield Zoo. Blood samples were obtained opportunistically from 275 individual animals immobilized for a variety of reasons; serum was analyzed for alpha- and beta-carotene, lutein + zeaxanthin, lycopene, beta-cryptoxanthin and canthaxanthin. Total carotenoid content of diets was calculated from tables and chemical analyses of commonly consumed dietary components. Diets were categorized as low, moderate or high in carotenoid content as were total serum carotenoid concentrations. Animals were classified as unknown, high, moderate or low (non-) accumulators of dietary cartenoids. Nonaccumulators had total serum carotenoid concentrations of 0-101 nmol/L, whereas accumulators had concentrations that ranged widely, from 225 to 35,351 nmol/L. Primates were uniquely distinguished by the widest range of type and concentration of carotenoids in their sera. Most were classified as high to moderate accumulators. Felids had high accumulation of beta-carotene regardless of dietary intake, whereas a wide range of exotic birds accumulated only the xanthophylls, lutein + zeaxanthin, canthaxanthin or cryptoxanthin. The exotic ungulates, with the exception of the bovids, had negligible or nondetectable carotenoid serum concentrations despite moderate intakes. Bovids accumulated only beta-carotene despite moderately high lutein + zeaxanthin intakes. Wild captive species demonstrated a wide variety of carotenoid accumulation patterns, which could be exploited to answer remaining questions concerning carotenoid metabolism and function.     

Interaction between dietary fat intake and the cholesterol ester transfer protein TaqIB polymorphism in relation to HDL-cholesterol concentrations among US diabetic men

BACKGROUND: A low plasma HDL-cholesterol concentration is a major characteristic of diabetic dyslipidemia. HDL concentrations are determined by both environmental factors and genetic factors. Cholesterol ester transfer protein (CETP) plays an important role in the regulation of HDL metabolism, and the TaqIB polymorphism of the CETP gene has been associated with elevated HDL concentrations. OBJECTIVE: We examined the association between the CETP TaqIB polymorphism and plasma HDL concentrations and evaluated whether this association was modified by dietary fat intake. DESIGN: We followed 780 diabetic men aged 40-75 y who participated in the Health Professionals Follow-Up Study since its initiation in 1986. The participants had confirmed type 2 diabetes and were free of cardiovascular disease at the time blood was drawn. RESULTS: After adjustment for age, smoking, alcohol consumption, fasting status, hemoglobin A(1c), physical activity, total energy intake, and body mass index, HDL concentrations were significantly higher in men with the B2B2 or B1B2 genotype than in those with the B1B1 genotype (adjusted x +/- SE: 37.9 +/- 0.02, 40.3 +/- 0.01, and 42.6 +/- 0.02 mg/dL for B1B1, B1B2, and B2B2, respectively; P for trend = 0.0004). This inverse association of the B1 allele with plasma HDL concentrations existed for those with a high consumption of animal fat (P for interaction = 0.02), saturated fat (P for interaction = 0.02), and monounsaturated fat (P for interaction = 0.04). CONCLUSION: These data confirmed a significant effect of the CETP Taq1 gene on HDL concentrations and suggested a potential interaction between the CETP TaqIB polymorphism and intake of dietary fat on plasma HDL concentration.     

胆固醇酯转移蛋白基因Taq1B多态性对高脂人群血清高密度脂蛋白胆固醇水平膳食易感性的作用

目的 探讨胆固醇酯转移蛋白（CETP）基因Taq1B位点多态性是否会影响高脂人群血清高密度脂蛋白胆固醇（HDL-C）对膳食因素的反应。方法 对上海市某社区141例高脂血症患者进行膳食调查,测定其血脂水平,以聚合酶链反应．限制性内切酶片段长度多态性（PCR-RFLP）测定调查对象CETP基因Taq1B位点的多态性,并在控制性别、年龄、体质指数的作用下,分析不同基因型高脂人群中膳食因素与血清HDL-C水平的关系。结果 高脂人群血清HDL-C同时受到膳食因素与CETP基因Taq 1B位点多态性的影响。在不同基因型人群中HDL-C与膳食因素的相关性不同,B2B2型中两者的相关性明显强于B1B1型。结论 CETP Taq1B多态性可能会影响高脂人群血清HDL-C对膳食干预的易感性。