脂负荷性饵食对家兔脂代谢的影响

目的探讨建立兔饵食性高脂血症模型的方法,观察高脂饮食对兔体重、死亡率及血脂变化情况。方法取普通级雄性新西兰大耳白兔,其中随机抽取10只作为普通饮食组,喂以普通饮食;其他动物给予高脂饮食,4周后,根据血清TC水平分为高脂饮食敏感组和高脂饮食非敏感组,继续喂养9周,观察三组间兔血清总胆固醇（TC）、甘油三脂（TG）、高密度脂蛋白胆固醇（HDL-C）和低密度脂蛋白胆固醇（LDL-C）的变化。结果与普通饮食组相比,高脂饮食敏感组在第4～13周时血清TC、TG、HDL-C、LDL-C水平显著升高（P〈0.01）,高脂饮食非敏感组在第7～13周时,动物血清TC、HDL-C、LDL-C水平显著升高（P〈0.01）,而高脂饮食非敏感组血清TG水平的改变无统计学意义（P〉0.05）。与高脂饮食敏感组相比,高脂饮食非敏感组家兔血清TC、TG、HDL-C和LDL-C水平的上升程度均显著低于高脂饮食敏感组动物（P〈0.01）。结论首次发现兔对高脂饮食敏感性存在差异,高脂饮食非敏感组家兔抗病能力、对环境的适应能力和耐受性均高于高脂饮食敏感组兔。与高脂饮食敏感组家兔相比,高脂饮食非敏感组家兔对高脂饮食耐受性强。     

山楂籽油降血脂作用研究

采用不同剂量山楂籽油对小鼠进行灌胃试验,研究其对血脂水平的影响。结果表明山楂籽油组小鼠的血清甘油三酯(TG),总胆固醇(TC),低密度脂蛋白胆固醇(LDL-C)和动脉硬化指数(AI)均不同程度(P<0.05或P<0.01)低于高脂模型组,而高密度脂蛋白胆固醇(HDL-C)却明显(P<0.01)高于高脂模型组,说明山楂籽油确具显著(P<0.05)降低小鼠血脂作用。     

三种金花茶提取物降脂作用实验研究

目的:探讨金花茶浓缩液、金花茶乙酸乙酯/二氯甲烷提取物以及金花茶水提物对高脂血症小鼠血脂的调节作用。方法:将小鼠按照体重随机分成正常饮食组和高脂饮食组,分别给予正常饲料和高脂饲料喂食,4周后将高脂饮食小鼠按照体重以及血脂水平(TC)随机分成金花茶浓缩液组、金花茶乙酸乙酯/二氯甲烷提取物组、金花茶水提物组以及辛伐他丁组。3种金花茶提取物以及辛伐他丁混悬液连续灌胃10周,同时给予高脂饮食。末次给药后禁食不禁水12 h,摘眼球取血,检测血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、超氧化物歧化酶(SOD)以及丙二醛(MDA)。结果:与模型组相比,金花茶浓缩液和辛伐他丁能显著降低血清TC、TG、LDL-C水平(P0.01或P0.05),但是对HDL-C无明显调节作用;对血清中的AST、ALT、SOD以及MDA影响不大。金花茶乙酸乙酯/二氯甲烷提取物以及水体物对血清中的TC、TG、LDL-C、HDL-C、AST、ALT、SOD及MDA无明显的调节作用。结论:金花茶浓缩液对高脂血症小鼠的血脂具有良好的调节作用。     

双歧杆菌培养上清调节D-半乳糖衰老小鼠血脂水平的实验研究

目的通过观察双歧杆菌培养上清（spent culture supernatant,SCS）对D-半乳糖所致亚急性衰老小鼠血脂指标和学习记忆行为的影响,探讨双歧杆菌培养上清减低血脂的机制,为进一步研究双歧杆菌培养上清中有效延缓衰老的成分提供理论依据。方法小鼠颈背部皮下注射生理盐水和D-半乳糖建立亚急性老年模型和正常对照,同时,对实验组小鼠腹腔注射双歧杆菌培养上清,连续培养42 d后称重,用跳台法对小鼠学习、记忆能力进行测试后断颈处死,检测血清中总胆固醇（TC）、甘油三酯（TG）和高密度脂蛋白（HDL-C）含量。结果与模型组相比,实验组小鼠血清TG、TC水平显著降低（P〈0.05）,血清HDL-C/TC水平明显提高,学习记忆能力较模型组也有明显提高。结论双歧杆菌上清能降低血清TG、TC含量,延缓D-半乳糖小鼠的衰老进程。     

菊苣提取物和菊粉降脂活性研究

以300日龄商品代尼克T粉壳蛋鸡为试验动物,研究了菊苣提取物和菊粉对血清脂质、蛋黄总脂和胆固醇的影响.结果显示,0.1%菊苣提取物组、2.0%菊苣提取物组和0.1%菊粉组血清胆固醇(TC)、甘油三脂(TG)、低密度脂蛋白(LDL-C)均显著低于对照组(P<0.05),其中0.1%菊苣提取物组TC降低36.47%,TG降低40.71%,LDL-C降低36.09%,0.1%菊粉组LDL-C降低16.23%,差异极显著(P<0.01);2.0%菊苣提取物组高密度脂蛋白(HDL-C)比对照组高23.19%,差异极显著(P<0.01);2.0%菊苣提取物组蛋黄总脂和蛋黄胆固醇显著降低(P<0.05).表明菊苣提取物和菊粉均具有降血脂活性,但菊苣提取物比菊粉活性更强;菊苣提取物还具有降低蛋黄总脂和胆固醇的作用.     

大头金蝇幼虫油脂对小鼠的降血脂作用

用健康昆明种小鼠建立高脂血症模型,同时用不同剂量的大头金蝇Chrysomyia megacepha la (Fabricius)幼虫油脂灌胃5周,摘除眼球取血,用试剂盒检测血脂值,光学显微镜观察小鼠肝脏病理变化。结果表明：大头金蝇幼虫油脂处理组小鼠血清胆固醇(TC)、甘油三酯（TG）、低密度脂蛋白胆固醇(LDL-C)水平显著降低,低剂量、中剂量和高剂量油脂处理组小鼠TG的浓度较高脂模型组小鼠分别下降20.70%、48.98%和56.06%;高脂模型组小鼠血清TC高达4.59 mmol/L,低剂量、中剂量和高剂量油脂处理组小鼠TC浓度较高脂模型组小鼠分别下降16.99%、23.52%和25.49%;高密度脂蛋白胆固醇（HDL-C）升高明显,低剂量、中剂量和高剂量油脂处理组小鼠HDL-C较高脂模型组小鼠升高11.74%、18.04%和18.95%,并呈现一定的剂量-效应关系;连续饲喂大头金蝇幼虫油脂对小鼠肝细胞有一定保护作用。提示大头金蝇幼虫油脂具有治疗小鼠高脂血症的作用。     

瑞舒伐他汀对兔动脉粥样硬化斑块及血清PAPP-A的影响

目的:探讨瑞舒伐他汀对兔动脉粥样硬化斑块及血清妊娠相关血浆蛋白(PAPP-A)的影响.方法:新西兰家兔18只,随机分为正常对照组(Normal组,n=6)、动物粥样梗化模型组(AS组,n=6)和瑞舒伐他汀治疗组(RSV组,n=6).于治疗前、治疗后,检测血清总胆固醇(TC)、三酰甘油(TG)、血清低密度脂蛋白胆固醇(LDL-C)及高密度脂蛋白胆固醇(HDL-C)含量,酶联免疲吸附法(ELISA)检测血清PAPP-A水平.同时,用血管内超声检查(IVUS)测定病变部位的血管外弹力膜面积(EEMA)、管腔面积(LA)和斑块面积(PA),计算管腔面积狭窄百分率(LAS%).结果:治疗前,AS组和RSV组兔的血清TC、TG、LDL-C及PAPP-A的水平较Normal组高(P<0.01),HDL-C的水平较Normal组低(P<0.01);治疗后,RSV组兔的血清TC、TG、LDL-C及PAPP-A比AS组低(P<0.01).HDL-C的水平比AS组高(P<0.01),且RSV组兔的血清TC、TG、LDL-C及PAPP-A的水平较治疗前低(P<0.01),HDL-C的水平较治疗前高(P<0.01).血管内超声检查结果显示,治疗后,RSV组兔的LAS%(30.87%±5.27%)比AS组低(37.42%±6.12%)(P<0.01).结论:瑞舒伐他汀能改善对AS兔血脂,减少AS斑块形成及降低血清PAPP-A水平.     

双歧醋对高脂饮食大鼠血脂的影响

目的 探讨双歧醋对高脂饮食大鼠血脂的影响作用.方法 48只SD大鼠被随机分成双歧醋低剂量组[1.8 mL/( kg·BW)]、中剂量组[3.4 mL/(kg · BW)]、高剂量组[6.8 mL/(kg · BW)]和市售醋组[3.4 mL/( kg·BW)]、高脂模型组以及正常组,观察双歧醋对高脂饮食大鼠血脂的影响作用,测定指标包括大鼠体重、肝指数、体脂指数、病理学观察肝脏脂肪变性等.结果 实验结果显示,双歧醋各组所有测定指标值都较高脂模型组有明显好转,特别是甘油三酯(TG)和高密度脂蛋白胆固醇(HDL-C)水平双歧杆菌醋的高、中量组与市售醋组比较差异有统计学意义(P＜0.05).结论 双歧醋能有效预防高脂饮食大鼠的血脂水平升高,对预防体重、肝指数升高和肝脏脂肪变性也有一定作用.     

有氧运动对小鼠高脂血症及脂蛋白代谢的影响

本研究以高胆固醇饮食小鼠为实验对象,观察有氧运动对脂质水平异常的动物个体血脂及脂蛋白代谢的影响。结果显示,经１１周有氧耐力训练后,高脂膳食＋运动组小鼠血浆ＴＧ、ＴＣ及ＬＤＬ－Ｃ水平均显著低于高脂膳食组（Ｐ＜０．０５）,而ＨＤＬ－Ｃ／ＴＣ和ＨＤＬ－Ｃ／ＬＤＬ－Ｃ比值均显著高于高脂膳食组（Ｐ＜０．０５）。表明长期有氧耐力训练能显著改善高胆固醇饮食小鼠血脂及脂蛋白代谢状况。     

金黄地鼠高血脂模型的建立

目的建立高血脂金黄地鼠动物模型,研究红葡萄酒预防高血脂的作用。方法用含有2%胆固醇的高脂饲料喂养金黄地鼠,设正常对照组和模型组,饲养15 d。期间观察金黄地鼠对高脂饲料的耐受性,试验结束时,测量血清总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、极低密度脂蛋白胆固醇(VLDL-C)值,并对肝脏进行光镜和电镜观察。结果金黄地鼠对高脂饲料具有较强的耐受性。经过15 d之后,模型组TC、TG、HDL-C、LDL-C、VLDL-C极显著升高(P<0.01),分别为对照组的9.06、4.19、2.43、6.21、18.88倍,而HDL-C/(LDL-C VLDL-C)显著降低(P<0.05),光镜和电镜观察表明模型组动物的肝脏出现脂肪肝样改变。结论本造型方法时间短,取血方便,血量充足,是一个较好的高血脂模型建立方法。     

Osbpl8 Deficiency in Mouse Causes an Elevation of High-Density Lipoproteins and Gender-Specific Alterations of Lipid Metabolism

OSBP-related protein 8 (ORP8) encoded by Osbpl8 is an endoplasmic reticulum sterol sensor implicated in cellular lipid metabolism. We generated an Osbpl8^−/− (KO) C57Bl/6 mouse strain. Wild-type and Osbpl8KO animals at the age of 13-weeks were fed for 5 weeks either chow or high-fat diet, and their plasma lipids/lipoproteins and hepatic lipids were analyzed. The chow-fed Osbpl8KO male mice showed a marked elevation of high-density lipoprotein (HDL) cholesterol (+79%) and phospholipids (+35%), while only minor increase of apolipoprotein A-I (apoA-I) was detected. In chow-fed female KO mice a less prominent increase of HDL cholesterol (+27%) was observed, while on western diet the HDL increment was prominent in both genders. The HDL increase was accompanied by an elevated level of HDL-associated apolipoprotein E in male, but not female KO animals. No differences between genotypes were observed in lecithin:cholesterol acyltransferase (LCAT) or hepatic lipase (HL) activity, or in the fractional catabolic rate of fluorescently labeled mouse HDL injected in chow-diet fed animals. The Osbpl8KO mice of both genders displayed reduced phospholipid transfer protein (PLTP) activity, but only on chow diet. These findings are consistent with a model in which Osbpl8 deficiency results in altered biosynthesis of HDL. Consistent with this hypothesis, ORP8 depleted mouse hepatocytes secreted an increased amount of nascent HDL into the culture medium. In addition to the HDL phenotype, distinct gender-specific alterations in lipid metabolism were detected: Female KO animals on chow diet showed reduced lipoprotein lipase (LPL) activity and increased plasma triglycerides, while the male KO mice displayed elevated plasma cholesterol biosynthetic markers cholestenol, desmosterol, and lathosterol. Moreover, modest gender-specific alterations in the hepatic expression of lipid homeostatic genes were observed. In conclusion, we report the first viable OsbplKO mouse model, demonstrating a HDL elevating effect of Osbpl8 knock-out and additional gender- and/or diet-dependent impacts on lipid metabolism.     

Effects of Dietary Korean Proso-Millet Protein on Plasma Adiponectin,HDL Cholesterol,Insulin Levels,and Gene Expression in Obese Type 2 Diabetic Mice

We investigated the effect of dietary Korean proso-millet protein concentrate (PMP) on glycemic responses, plasma lipid levels, and the plasma level and gene expression of adiponectin in obese type 2 diabetic mice under normal and high-fat feeding conditions. The findings were that the feeding of PMP clearly elevated plasma high-density lipoprotein cholesterol (HDL cholesterol) and adiponectin levels and brought about effective reduction in the levels of glucose and insulin in mice under high-fat diet conditions as compared with a control diet. Gene expression study revealed that the diet up-regulated expression of adiponectin and down-regulated tumor necrosis factor-α (TNF-α). Considering the central role of adiponectin and HDL cholesterol in improving and ameliorating type 2 diabetes, obesity, and cardiovascular disease, our findings imply that PMP may have potential for therapeutic intervention in type 2 diabetes.     

Effects of dietary Korean proso-millet protein on plasma adiponectin, HDL cholesterol, insulin levels, and gene expression in obese type 2 diabetic mice

We investigated the effect of dietary Korean proso-millet protein concentrate (PMP) on glycemic responses, plasma lipid levels, and the plasma level and gene expression of adiponectin in obese type 2 diabetic mice under normal and high-fat feeding conditions. The findings were that the feeding of PMP clearly elevated plasma high-density lipoprotein cholesterol (HDL cholesterol) and adiponectin levels and brought about effective reduction in the levels of glucose and insulin in mice under high-fat diet conditions as compared with a control diet. Gene expression study revealed that the diet up-regulated expression of adiponectin and down-regulated tumor necrosis factor-alpha (TNF-alpha). Considering the central role of adiponectin and HDL cholesterol in improving and ameliorating type 2 diabetes, obesity, and cardiovascular disease, our findings imply that PMP may have potential for therapeutic intervention in type 2 diabetes.     

Enterocyte-specific ATGL overexpression affects intestinal and systemic cholesterol homeostasis

Enterocytes of the small intestine (SI) play an important role in maintaining systemic lipid levels by regulating dietary lipid absorption and postprandial lipoprotein secretion. An excessive amount of dietary-derived triglycerides (TGs) taken up by the apical side of enterocytes or basolaterally internalized lipoprotein remnants can be transiently stored in cytosolic lipid droplets (cLDs). As mice lacking adipose TG lipase (ATGL) in the SI display massive accumulation of cLDs but also delayed cholesterol absorption, we hypothesized that SI-specific overexpression of ATGL (Atgl iTg) might have beneficial effects on lipid homeostasis in the gut and possibly throughout the body. Here, we demonstrate that Atgl iTg mice had only modestly increased enzymatic activity despite drastically elevated Atgl mRNA levels (up to 120-fold) on chow diet, and was highly induced upon high-fat/high-cholesterol diet (HF/HCD) feeding. Atgl iTg mice showed markedly reduced intestinal TG concentrations after acute and chronic lipid challenge without affecting chylomicron TG secretion. Circulating plasma cholesterol levels were significantly lower in Atgl iTg mice under different feeding conditions, contrasting the accelerated uptake of dietary cholesterol into the circulation after HF/HCD feeding. In the fasted state, gene expression analysis revealed modulation of PPARα and liver X receptor (LXR) target genes by an increased fatty acid release, whereas the decreased plasma cholesterol concentrations in refed mice were more likely due to changes in HDL synthesis and secretion. We conclude that ATGL, in addition to its role in TG catabolism, plays a critical role in whole-body cholesterol homeostasis by modulating PPARα and LXR signaling in intestinal enterocytes.     

Lipolysis stimulated lipoprotein receptor: a novel molecular link between hyperlipidemia, weight gain, and atherosclerosis in mice

The lipolysis-stimulated lipoprotein receptor, LSR, is a multimeric protein complex in the liver that undergoes conformational changes upon binding of free fatty acids, thereby revealing a binding site (s) that recognizes both apoB and apoE. Complete inactivation of the LSR gene is embryonic lethal in mice. Here we show that removal of a single LSR allele (LSR(-/+)) caused statistically significant increases in both plasma triglyceride and cholesterol levels, a 2-fold increase in plasma triglyceride changes during the post-prandial phase, and delayed clearance of lipid emulsions or a high fat meal. The longer postprandial lipoprotein clearance time observed in LSR(-/+) mice was further increased in LSR(-/+) mice lacking functional low density lipoprotein (LDL) receptors. LSR(-/+) mice placed on a Western-type diet displayed higher plasma triglycerides and cholesterol levels, increased triglyceride-rich lipoproteins and LDL, and increased aorta lipid content, as compared with control mice on the same diet. Furthermore, a direct correlation was observed between the hyperlipidemia and weight gain but only in the LSR(-/+) mice. Knockdown of LSR expression by small interfering RNA in mouse Hepa1-6 cells led to decreased internalization of both DiI-labeled cyclohexanedione-LDL and very low density lipoprotein in the presence of oleate. These data led us to conclude that LSR contributes to the physiological clearance of atherogenic triglyceride-rich lipoproteins and LDL. We propose that LSR cooperates with the LDL receptor in the final hepatic processing of apoB-containing lipoproteins and represents a novel therapeutic target for the treatment of hyperlipidemia associated with obesity and atherosclerosis.     

Increased Hepatic Lipogenesis Elevates Liver Cholesterol Content

Cardiovascular diseases (CVDs) are the most common cause of death in patients with nonalcoholic fatty liver disease (NAFLD) and dyslipidemia is considered at least partially responsible for the increased CVD risk in NAFLD patients. The aim of the present study is to understand how hepatic de novo lipogenesis influences hepatic cholesterol content as well as its effects on the plasma lipid levels. Hepatic lipogenesis was induced in mice by feeding a fat-free/high-sucrose (FF/HS) diet and the metabolic pathways associated with cholesterol were then analyzed. Both liver triglyceride and cholesterol contents were significantly increased in mice fed an FF/HS diet. Activation of fatty acid synthesis driven by the activation of sterol regulatory element binding protein (SREBP)-1c resulted in the increased liver triglycerides. The augmented cholesterol content in the liver could not be explained by an increased cholesterol synthesis, which was decreased by the FF/HS diet. HMG-CoA reductase protein level was decreased in mice fed an FF/HS diet. We found that the liver retained more cholesterol through a reduced excretion of bile acids, a reduced fecal cholesterol excretion, and an increased cholesterol uptake from plasma lipoproteins. Very low-density lipoprotein-triglyceride and -cholesterol secretion were increased in mice fed an FF/HS diet, which led to hypertriglyceridemia and hypercholesterolemia in Ldlr^-/- mice, a model that exhibits a more human like lipoprotein profile. These findings suggest that dietary cholesterol intake and cholesterol synthesis rates cannot only explain the hypercholesterolemia associated with NAFLD, and that the control of fatty acid synthesis should be considered for the management of dyslipidemia.     

Effects of dietary protein of Korean foxtail millet on plasma adiponectin, HDL-cholesterol, and insulin levels in genetically type 2 diabetic mice

We examined the effects of intake of Korean foxtail millet protein (FMP) on plasma levels of lipid, glucose, insulin, and adiponectin in genetically type 2 diabetic KK-Ay mice. When mice were fed a normal FMP diet or a high-fat-high-sucrose diet containing FMP for 3 weeks, in both experiments plasma concentrations of high-density lipoprotein cholesterol (HDL-cholesterol) and adiponectin increased remarkably in comparison with a casein diet group, whereas concentrations of insulin decreased greatly and that of plasma glucose was comparable to that in the casein diet group. Considering the role of adiponectin, insulin, and HDL-cholesterol in diabetes, atherosclerosis, and obesity, it appears likely that FMP may improve insulin sensitivity and cholesterol metabolism through an increase in adiponectin concentration. Therefore, FMP would serve as another beneficial food component in obesity-related diseases such as type 2 diabetes and cardiovascular diseases.     

Effects of phenotype, sex, and diet on plasma lipids in LA/N-cp rats

The LA/N-corpulent (cp) rat is a recently developed congenic strain which exhibits obesity. The effects of phenotype and sex on serum and lipoprotein lipid content were examined in LA/N-cp rats fed either a control or an atherogenic diet high in saturated fat and protein. Obese rats were pair-fed to equivalent lean animals. Results from this study indicate that sex, phenotype, and diet exert significant effects on plasma and lipoprotein cholesterol content. Plasma cholesterol levels were higher in obese compared with lean rats, females than in males, and rats consuming the atherogenic diet compared with the control diet. Plasma and lipoprotein triglyceride levels were significantly increased only in obese compared with lean animals. The increased plasma cholesterol and triglyceride was observed primarily in the chylomicron and very low density lipoprotein fractions. Increased levels of plasma cholesterol were not a result of increased dietary cholesterol absorption or increased liver cholesterol biosynthesis. These data suggest that LA/N-cp rats can serve as a unique rodent model for the study of the interrelationships between hyperlipidemia, obesity, and coronary heart disease.     

Effect of dietary lipids on plasma lipoproteins and fluidity of lymphoid cell membranes in normal and leukemic mice

Mice of the GR/A strain were fed four different isocaloric semipurified diets, enriched in either (1) saturated fatty acids (palm oil), or (2) polyunsaturated fatty acids (corn oil), or (3) palm oil plus cholesterol, or (4) a fat-poor diet containing only a minimal amount of essential fatty acids. We have studied the effects of these dietary lipids on the density profile and composition of the plasma lipoproteins and on the lipid composition and fluidity of (purified) lymphoid cell membranes in healthy mice and in mice bearing a transplanted lymphoid leukemia (GRSL). Tumor development in these mice occurred in the spleen and in ascites. While the fatty acid composition of the VLDL-triacylglycerols still strongly resembled the dietary lipids, the effects of the diets decreased in the order VLDL-triacylglycerols greater than HDL-phospholipids greater than plasma membrane phospholipids. Diet-induced differences in the latter fraction were virtually confined to the content of oleic acid and linoleic acid, and they were too small to affect the membrane fluidity, as measured by fluorescence polarization using the probe 1,6-diphenyl-1,3,5-hexatriene. Healthy mice were almost irresponsive to dietary cholesterol, but in the tumor bearers, where lipoprotein metabolism has been shown to be disturbed, the cholesterol diet caused a substantial increase in the low- and very-low density regions of both blood and ascites plasma lipoproteins. The cholesterol-rich diet also increased the cholesterol/phospholipid molar ratio and lipid structural order (decreased fluidity) in GRSL ascites cell membranes, but not in the splenic GRSL cell membranes. We conclude that the composition of plasma lipoproteins and cell membrane lipids in GR/A mice is subject to exquisite homeostatic control. However, in these low-responders to dietary lipids the development of an ascites tumor may lead to increased responsiveness to dietary cholesterol. The elevated level of membrane cholesterol thus obtained in GRSL ascites cells did not affect the expression of various cell surface antigens or tumor cell growth.     

Global functional knockdown of ATP binding cassette transporter A1 stimulates development of atherosclerosis in apoE K/O mice

ABCA1 is a key element of cellular cholesterol homeostasis. ApoE K/O mice fed with high-fat diet were infused with anti-ABCA1 antibody or control IgM. Infusion of anti-ABCA1 antibody led to 72% increase in the area of atherosclerotic plaque in aorta. After 16 weeks on high-fat diet plasma level of high density lipoprotein cholesterol (HDL-C) was reduced in control group, but was unchanged in mice infused with anti-ABCA1 antibody. Total plasma cholesterol level was elevated while the capacity of plasma to support cholesterol efflux ex vivo was reduced after 16 weeks on high-fat diet; the effects were similar in the two groups. We conclude that functional blocking of ABCA1-dependent cholesterol efflux stimulates development of atherosclerosis in apoE K/O mice independently from HDL-C levels.