| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Lipid dynamics and domain formation in model membranes composed of ternary mixtures of unsaturated and saturated phosphatidylcholines and cholesterol Scherfeld, D., N. Kahya, et al. (2003), Biophys J 85(6): 3758-68. Abstract: In recent years, the implication of sphingomyelin in lipid raft formation has intensified the long sustained interest in this membrane lipid. Accumulating evidences show that cholesterol preferentially interacts with sphingomyelin, conferring specific physicochemical properties to the bilayer membrane. The molecular packing created by cholesterol and sphingomyelin, which presumably is one of the driving forces for lipid raft formation, is known in general to differ from that of cholesterol and phosphatidylcholine membranes. However, in many studies, saturated phosphatidylcholines are still considered as a model for sphingolipids. Here, we investigate the effect of cholesterol on mixtures of dioleoyl-phosphatidylcholine (DOPC) and dipalmitoyl-phosphatidylcholine (DPPC) or distearoyl-phosphatidylcholine (DSPC) and compare it to that on mixtures of DOPC and sphingomyelin analyzed in previous studies. Giant unilamellar vesicles prepared from ternary mixtures of various lipid compositions were imaged by confocal fluorescence microscopy and, within a certain range of sterol content, domain formation was observed. The assignment of distinct lipid phases and the molecular mobility in the membrane bilayer was investigated by fluorescence correlation spectroscopy. Cholesterol was shown to affect lipid dynamics in a similar way for DPPC and DSPC when the two phospholipids were combined with cholesterol in binary mixtures. However, the corresponding ternary mixtures exhibited different spatial lipid organization and dynamics. Finally, evidences of a weaker interaction of cholesterol with saturated phosphatidylcholines than with sphingomyelin (with matched chain length) are discussed. |
| Lipid levels. Applying the second National Cholesterol Education Program report to geriatric medicine Mormando, R. M. (2000), Geriatrics 55(8): 48-53; quiz 54. Abstract: Aging is accompanied by increases in cholesterol levels that increase the risk of atherosclerosis, coronary heart disease, and stroke. A large body of evidence shows that lipid lowering can reduce the incidence of vascular-related events. Guidelines for the management of hypercholesterolemia were outlined in the second National Cholesterol Education Program report (Adult Treatment Panel II). According to ATPII, the first step is to identify individuals at risk for vascular disease and those with borderline-high or high cholesterol levels. Screening for hyperlipidemia should continue beyond age 65 if the individual patient would benefit from long-term lipid management. Primary and secondary interventions consist of dietary therapy, exercise, and pharmacotherapy, based on the individual patient's risk factors. |
| Lipid lowering activity of drugs affecting cholesterol absorption Norata, G. D. and A. L. Catapano (2004), Nutr Metab Cardiovasc Dis 14(1): 42-51. Abstract: AIM: Dietary cholesterol absorption, endogenous cholesterol synthesis and biliary cholesterol excretion regulate whole body cholesterol balance as a result of biotransformation into bile acids or direct cholesterol excretion. Recent studies have significantly advanced our understanding of intestinal sterol absorption at molecular level. This review concentrates on two major issues: the mechanisms of sterol absorption, and the currently available or experimental drugs that affect this pathway. DATA SYNTHESIS: Nuclear hormone receptors, such as the liver X, farnesoid X and retinoid X receptors, regulate the absorption of dietary sterols by modulating the transcription of several genes involved in cholesterol metabolism, The ABC proteins transport dietary cholesterol from enterocytes back to the intestinal lumen, thus limiting the amount of absorbed cholesterol. By means of the same mechanism, ABC transporters also provide an efficient barrier against the absorption of plant sterols. Phytosterols, bile acid sequestrants, ezetimibe and ACAT inhibitors are possible means of affecting these pathways. CONCLUSION: In addition to providing an insight into the molecular mechanisms of sterol absorption, these recent findings may lead to new therapeutic options for the treatment of hypercholesterolemia. This is particularly true in the case of patients at high risk of coronary artery disease requiring aggressive lipid-lowering therapy combining a statin with drugs affecting cholesterol absorption in order to ensure the optimal management of dyslipidemia. |
| Lipid lowering and beyond: results from the CARE study on lipoproteins and inflammation. Cholesterol and Recurrent Events Sacks, F. M. and P. M. Ridker (1999), Herz 24(1): 51-6. Abstract: The plasma LDL concentration in firmly established as a cause of coronary heart disease. However, the efficacy of LDL lowering may reach a limit when it is brought well below average during treatment. The Cholesterol and Recurrent Events (CARE) trial compared pravastatin and placebo in patients who had experienced myocardial infarction who had average concentrations of total cholesterol < 240 mg/dl (baseline mean 209 mg/dl) and LDL cholesterol (LDL) 115 to 174 mg/dl (mean 139 mg/dl). Pravastatin reduced coronary death or recurrent myocardial infarction by 24%. In multivariate analysis, the LDL concentration achieved during follow-up was a significant predictor of the coronary event rate. The relationship was nonlinear since the coronary event rate declined as LDL decreased during follow-up from 174 to approximately 125 mg/dl, but no further decline was seen in the LDL range from 125 to 71 mg/dl. A major ongoing effort in the CARE trial concerns the identification of non-LDL mediated mechanisms of coronary events. Chronic low-grade inflammation has recently been identified as an important new risk factor for coronary artery disease. Two markers of inflammation, C-reactive protein (CRP) and serum amyloid A (SAA), were measured in patients in the CARE trial who suffered a recurrent myocardial infarction or coronary death and in those who did not have these recurrent events. Levels of both inflammatory markers were significantly higher among post-myocardial infarction patients who subsequently developed recurrent coronary events. This association was significant in the patients who were treated with placebo but not in those in the pravastatin group. In conclusion, attaining an LDL of < 125 mg/dl may be sufficient treatment of LDL concentrations, removing the adverse effect of LDL on coronary events. These findings also raise the possibility that the efficacy of pravastatin may partly result from anti-inflammatory as well as lipid lowering properties. |
| Lipid lowering in post-MI patients with normal cholesterol Lawless, C. and R. Force (1997), J Fam Pract 44(1): 30. |
| Lipid metabolism disorder: detection and treatment. 5: Treatment of hyperlipidemia in manifest coronary heart disease, diabetes mellitus and hypertension. National cholesterol initiative Assmann, G. (1991), Fortschr Med 109(17): 361-3. |
| Lipid metabolism in hypercholesterolemic rats affected by feeding cholesterol-free diets containing different amounts of non-dialyzed soybean protein fraction Chen, J. R., S. F. Chiou, et al. (2003), Nutrition 19(7-8): 676-80. Abstract: OBJECTIVE: We investigated lipid metabolism in hypercholesterolemic rats after replacing casein with different amounts of undialyzed soybean protein fraction. METHODS: The hypercholesterolemic rats were fed cholesterol-free diets containing 2%, 5%, or 10% undialyzed soybean protein fraction (UDSP) for 4 wk. RESULTS: The 5% and 10% UDSP groups had significantly lower plasma cholesterol, triacylglycerol, and low-density lipoprotein cholesterol concentrations than did the other groups (P < 0.05). In addition, significantly higher fecal total steroid excretion was observed in these two groups. However, the different amounts of UDSP did not influence liver lipid, plasma high-density lipoprotein cholesterol, body weight gain, daily food intake, or feeding efficiency. CONCLUSION: These results suggested a dose-dependent reduction in plasma cholesterol when casein was replaced stepwise with UDSP (5% or 10%) as a protein source. The hypocholesterolemic effect might have been due to an increase in total fecal steroid excretion. |
| Lipid metabolism in Norplant-2 users--a two-year follow-up study. Total cholesterol, triglycerides, lipoproteins and apolipoproteins Rabe, T., H. C. Thuro, et al. (1992), Contraception 45(1): 21-37. Abstract: Changes in lipid metabolism in 25 healthy female volunteers during a 24-month application of Norplant-2 were evaluated in an open clinical trial. Total serum cholesterol decreased significantly (p less than 0.05/p less than 0.05) by 10%/9% after 12 months and by 3%/7% (n.s./n.s.) after 24 months of Norplant-2 use (all subjects/subjects completing 24 cycles). Serum triglycerides decreased by 34%/28% (n.s./p less than 0.05) after 12 months and by 29%/25% (p less than 0.05/p less than 0.05) after 24 months of Norplant-2 use (all subjects/subjects completing 24 cycles). HDL-cholesterol decreased significantly by 18%/12% (p less than 0.01/p less than 0.05) after 12 months and by 12%/12% (p less than 0.05/p less than 0.05) after 24 months of Norplant-2 use (all subjects/subjects completing 24 cycles). No statistically significant difference between serum levels of LDL-cholesterol prior to and after 12 and 24 months of Norplant-2 use could be found. VLDL-cholesterol levels decreased significantly by 38%/38% (p less than 0.05) after 12 and by 25%/25% after 24 months of Norplant-2 application (p less than 0.01) (all subjects/subjects completing 24 cycles). Apolipoprotein Al decreased significantly by 23%/23% (p less than 0.001/p less than 0.01) after 12 and by 21%/22% after 24 months of Norplant-2 application (p less than 0.01/p less than 0.01) (all subjects/subjects completing 24 cycles). No statistically significant difference between apolipoprotein All levels prior to and after 12 and 24 months of Norplant-2 implantation could be found. Apolipoprotein B decreased significantly by 27%/17% (p less than 0.05/p less than 0.05) after 12 months of Norplant-2 application (all subjects/subjects completing 24 cycles). The decline after 24 months of Norplant-2 use was not significant. Changes in lipid metabolism caused by oral hormonal contraceptives differ in the various clinical trials; however, most investigators found that serum levels of total cholesterol and triglycerides increase under the application of OCs. Contrary to this, a decrease of total cholesterol and triglycerides under Norplant-2 use was noted. Furthermore, we found a significant decrease of lipoproteins and apolipoproteins--with the exception of LDL-cholesterol and apolipoprotein All, which did not show any significant modifications. Thus, Norplant-2 seems to be non-contributory to cardiovascular risk and might even provide protection against such risks. |
| Lipid metabolism is altered by nebacitin in rats fed cooked-stored polished rice as the only dietary carbohydrate with or without exogenous cholesterol Cheng, H. H. and W. W. Yu (1997), J Nutr 127(1): 153-7. Abstract: Male adult Wistar rats were randomly divided into four groups in a 2 x 2 factorial design and were fed diets containing cooked-stored polished rice (CSPR), with and without 0.7 g/100 g of Nebacitin bacitracinneomycin sulfate (2:1, wt/wt) and with and without 1 g cholesterol/100 g diet. The CSPR diet contained 1.87 g resistant starch/100 g. After 4 wk, arterial blood and liver were collected. Feces were collected during the last 7 d. Rats fed the diet with Nebacitin and cholesterol had higher serum total cholesterol than the rats fed diets without cholesterol. Serum triglyceride concentration was greater in rats fed Nebacitin, regardless of dietary cholesterol concentration. Rats fed the diet with Nebacitin and cholesterol had higher serum LDL cholesterol concentration and liver total cholesterol concentration than rats fed the other three diets. Rats fed the CSPR diet with Nebacitin both with and without cholesterol had a higher fecal resistant starch concentration and excretion and lower serum short-chain fatty acid concentration than rats fed the diets without Nabacitin. Hepatic cholesterol concentration was greater in rats fed Nebacitin only when the diet also contained cholesterol. Therefore, dietary Nebacitin alters lipid metabolism in rats, and some effects are most pronounced in those also fed cholesterol. |
| Lipid modulation of the activity of diacylglycerol kinase alpha- and zeta-isoforms: activation by phosphatidylethanolamine and cholesterol Fanani, M. L., M. K. Topham, et al. (2004), Biochemistry 43(46): 14767-77. Abstract: Diacylglycerol kinase (DGK) isoforms alpha and zeta were extracted from transfected cells that overexpressed these enzymes. We determined the lipid dependence of the binding of these isoforms to liposomes. The modulation by lipid of the rate of phosphorylation of diacylglycerol by these enzymes was also measured. Incorporation of phosphatidylethanolamine into the liposomes resulted in an increased partitioning of both isoforms of DGK to the membrane as well as an increased catalytic rate. We demonstrate that the increased catalytic rate is a consequence of both increased portioning of the enzyme to the membrane and increased catalytic activity of the membrane-bound form. DGKalpha, a calcium-dependent isoform, can be activated in a calcium-independent fashion in the presence of phosphatidylethanolamine. Similar effects are observed with cholesterol. In contrast, sphingomyelin inhibits the activity of both isoforms of DGK. Our results demonstrate that the translocation to membranes and activity of DGKalpha and DGKzeta are modulated by the composition and properties of the membrane. The enzymes are activated by the presence of lipids that promote the formation of inverted phases. However, the promotion of negative curvature is not the sole factor contributing to the lipid effects on enzyme binding and activity. A truncated form of DGKalphalacking both the E-F hand and the recoverin homology domain is constitutively active and is not further activated by any of the lipids tested or by calcium. However, a truncated form lacking only the recoverin homology domain is partially activated by either calcium or certain lipids. |
| Lipid peroxidation in different tissues: effect of high cholesterol and fish oil in the diet Upadhya, S., Kavitha, et al. (2002), Indian J Physiol Pharmacol 46(4): 475-81. Abstract: Malonyldialdehyde was measured in erythrocytes, aorta and spleen on feeding mice with high cholesterol diet in presence and absence of fish oil. Mice were grouped as: Group I: Control laboratory diet Group II: 0.16% cholesterol (sunflower oil) Group III: 1.16% cholesterol (sunflower oil) Group IV: 1.16% cholesterol (fish oil) After 7 weeks on their respective diets, erythrocytic, and splenic MDA levels were significantly higher in group III compared to controls. Also, MDA levels in aorta and spleen showed a significant increase in group IV males compared to group III males. However in group IV the erythrocyte MDA levels were almost equal to that in controls. This suggests that high cholesterol diet increases lipid peroxidation in erythrocytes, spleen and aorta. Addition of fish oil in the diet further increases lipid peroxidation in aorta and spleen, but not in the erythrocytes. |
| Lipid peroxidation in photodynamically stressed mammalian cells: use of cholesterol hydroperoxides as mechanistic reporters Geiger, P. G., W. Korytowski, et al. (1997), Free Radic Biol Med 23(1): 57-68. Abstract: Photodynamic action of merocyanine 540, an antileukemic sensitizing dye, on murine L1210 cells results in the formation of lipid hydroperoxides and loss of cell viability. High-performance liquid chromatography with mercury cathode electrochemical detection was used for determining lipid oxidation products, including the following cholesterol-derived hydroperoxides: 5 alpha-OOH, 6 alpha-OOH, 6 beta-OOH, and unresolved 7 alpha, 7 beta-OOH. Among these species, 5 alpha-, 6 alpha-, and 6 beta-OOH (singlet oxygen adducts) were predominant in the early stages of photooxidation, whereas 7 alpha- and 7 beta-OOH (products of free radical reactions) became so after prolonged irradiation or during dark incubation after exposure to a light dose. These mechanistic changes were studied in a unique way by monitoring shifts in the peroxide ratio, i.e., 7-OOH/5 alpha-OOH, or 7-OOH/6-OOH. When cells (10(7)/ml) were exposed to a visible light fluence of 0.6 J/cm2 in the presence of 10 microM merocyanine 540, 7-OOH/5 alpha-OOH increased by approximately 100% after 2 h of dark incubation at 37 degrees C. The increase was much larger (approximately 250%) when cells were photooxidized after treatment with 1 microM ferric-8-hydroxyquinoline, a lipophilic iron donor, whereas no increase was observed when cells were pretreated with 100 microM desferrioxamine, an avid iron chelator/redox inhibitor. Correspondingly, postirradiation formation of thiobarbituric acid-reactive material was markedly enhanced by ferric-8-hydroxyquinoline and suppressed by desferrioxamine, as was the extent of cell killing. When added to cells after a light dose, chain-breaking antioxidants such as butylated hydroxytoluene and alpha-tocopherol strongly protected against cell killing and slowed the increase in 7-OOH/5 alpha-OOH ratio. It is apparent from these results that (1) the 7-OOH/5 alpha-OOH or 7-OOH/6-OOH ratio can be used as a highly sensitive index of singlet oxygen vs. free radical dominance in photodynamically stressed cells; and (2) that postirradiation chain peroxidation plays an important role in photodynamically initiated cell killing. |
| Lipid peroxidation of microsomal and mitochondrial membranes extracted with n-pentane and reconstituted with ubiquinol, dolichol and cholesterol Jakobsson-Borin, A., F. Aberg, et al. (1994), Biochim Biophys Acta 1213(2): 159-66. Abstract: Microsomes and mitochondria prepared from rat liver were extracted with n-pentane, a procedure which does not denature enzyme proteins. Protein and phospholipid were not extracted, but 75-80% of the total dolichol, 80-100% of the ubiquinone and 85-95% of the cholesterol were removed from both organelles by this procedure. Enzymatic and non-enzymatic lipid peroxidation in microsomes and non-enzymatic peroxidation in mitochondria were strongly inhibited when ubiquinol was reinserted into n-pentane-extracted membranes. When reconstitution with dolichol was performed, lipid peroxidation was increased or unchanged, while cholesterol decreased this activity in a concentration-dependent manner. In reconstitution experiments ubiquinol and dolichol together were less inhibitory than ubiquinol alone, whereas cholesterol accentuated the inhibitory effect of ubiquinol. Reconstitution with dolichols of different lengths, dolichyl esters or with alpha-unsaturated polyprenols further demonstrated that dolichol is not an antioxidant. It appears that mevalonate pathway lipids influence lipid peroxidation in membranes by modifying the properties of the bilayer. |
| Lipid peroxidative damage in the erythrocytes and elevation of serum LDL-cholesterol, apolipoprotein-B, ferritin and uric acid with age and in coronary heart disease patients El-Gebali, H. H., S. A. Tahir, et al. (2000), Saudi Med J 21(2): 184-9. Abstract: OBJECTIVES: To determine the normal serum levels of LDL-cholesterol, apolipoprotein-B, ferritin, uric acid, and the extent of erythrocytes lipid peroxidation in healthy control group subjects and to compare them with coronary heart disease patients. Secondly, to study the effects of age and sex on these parameters. METHODS: The blood samples from 150 healthy Libyan control group subjects (110 men and 40 women) were classified into 3 groups according to their age. Group I consisted of 76 subjects with an age range from 20 to 35 years. Group II consisted of 45 subjects with an age range from 36 to 50 years. Group III consisted of 29 subjects with an age range from 51 to 74 years. The blood samples from these groups were analyzed for LDL-cholesterol, apolipoprotein-B, ferritin and uric acid levels. Lipid peroxidation was compared in the erythrocytes of 56 selected healthy control group subjects (31 men and 11 women) of the aforementioned age groups. RESULTS: These parameters have shown age-dependent elevation in their levels. Meanwhile, LDL-cholesterol and Apolipoprotein-B levels in female subjects were higher than those of males. However, lipid peroxidation in the erythrocytes has revealed a statistically significant increase with increasing age. The comparison between 93 selected, sex and age matched, healthy control group subjects with 87 selected coronary heart disease patients (55 men and 45 women) with an age range from 30 to 74 years (49.6+13.25) has demonstrated significantly higher concentration of LDL-cholesterol, Apolipoprotein-B, ferritin and uric acid in coronary heart disease patients than those of healthy control group subjects. Meanwhile, lipid peroxidation was also significantly enhanced in coronary heart disease patients compared with healthy control group subjects. CONCLUSION: Our study has revealed that an increase in the lipid peroxidation in erythrocytes with age and during coronary heart disease, makes red cell membranes more vulnerable to free radical damage via formation of reactive oxygen species. It is thus likely that peroxidative damage may be contributing to an increase in serum LDL-cholesterol, Apolipoprotein-B, probably after its oxidative modification, increase in ferritin and hyperuricemia in coronary heart disease patients. |
| Lipid profile in the hyperacute phase of ischemic stroke allows to decide cholesterol-lowering therapy Delgado Martinez, P., J. Montaner Villalonga, et al. (2005), Med Clin (Barc) 124(8): 295-7. Abstract: BACKGROUND AND OBJECTIVE: We aimed to determine whether measuring the hyperacute lipid profile helps to start a cholesterol-lowering therapy soon after an ischemic stroke. PATIENTS AND METHOD: 72 ischemic stroke patients underwent lipid determinations at three times (hyperacute phase or arrival, second day and the third month). RESULTS: Total cholesterol, cLDL, cHDL and triglyceride mean values were significantly higher (p < 0.05) at arrival compared to the second day (212 vs 189; 131 vs 120; 52 vs 44 and 132 vs 115, respectively). In the third month, mean values were similar to those of the hyperacute phase (197, 131, 48 and 143, respectively). Considering the updated cholesterol management guidelines, we should treat 55% of patients diagnosed at the hyperacute phase but only 37% of patients diagnosed at the second day. CONCLUSION: Hyperacute lipid profile determination helps to determine those patients who need a cholesterol-lowering therapy without delay. |
| Lipid rafts and HIV pathogenesis: host membrane cholesterol is required for infection by HIV type 1 Liao, Z., L. M. Cimakasky, et al. (2001), AIDS Res Hum Retroviruses 17(11): 1009-19. Abstract: In a previous study we showed that budding of HIV-1 particles occurs at highly specialized membrane microdomains known as lipid rafts. These microdomains are characterized by a distinct lipid composition that includes high concentrations of cholesterol, sphingolipids, and glycolipids. Since cholesterol is known to play a key role in the entry of some other viruses, our observation of HIV budding from lipid rafts led us to investigate the role in HIV-1 entry of cholesterol and lipid rafts in the plasma membrane of susceptible cells. We have used 2-OH-propyl-beta-cyclodextrin (beta-cyclodextrin) to deplete cellular cholesterol and disperse lipid rafts. Our results show that removal of cellular cholesterol rendered primary cells and cell lines highly resistant to HIV-1-mediated syncytium formation and to infection by both CXCR4- and CCR5-specific viruses. beta-Cyclodextrin treatment of cells partially reduced HIV-1 binding, while rendering chemokine receptors highly sensitive to antibody-mediated internalization. There was no effect on CD4 expression. All of the above-described effects were readily reversed by incubating cholesterol-depleted cells with low concentrations of cholesterol-loaded beta-cyclodextrin to restore cholesterol levels. Cholesterol depletion made cells resistant to SDF-1-induced binding to ICAM-1 through LFA-1. Since LFA-1 contributes significantly to cell binding by HIV-1, this latter effect may have contributed to the observed reduction in HIV-1 binding to cells after treatment with beta-cyclodextrin. Our results indicate that cholesterol may be critical to the HIV-1 coreceptor function of chemokine receptors and is required for infection of cells by HIV-1. |
| Lipid rafts and HIV pathogenesis: virion-associated cholesterol is required for fusion and infection of susceptible cells Liao, Z., D. R. Graham, et al. (2003), AIDS Res Hum Retroviruses 19(8): 675-87. Abstract: We have shown that HIV budding occurs at cholesterol-rich membrane microdomains called lipid rafts (Nguyen and Hildreth, J Virol 2000;74:3264-3272). This observation prompted us to examine the role in HIV entry of cholesterol in the membrane of cells. We recently reported that host cell cholesterol is required for HIV infection (Liao et al., AIDS Res Hum Retroviruses 2001;17:1009-1019). In the present study we examined the role of virion-associated cholesterol in HIV infection by modulating the cholesterol content of virions and infected cells with 2-hydoxypropyl-beta-cyclodextrin (beta-cyclodextrin). Our results show that removal of cholesterol from the membrane of HIV-infected cells dramatically lowered virus release and that virions released from cholesterol-depleted cells are minimally infectious. Exposure of infectious HIV particles to beta-cyclodextrin resulted in a dose-dependent inactivation of the virus. In both cases, the effect was attributable to loss of cholesterol and could be reversed by replenishing cholesterol. beta-Cyclodextrin-treated, noninfectious HIV retained its ability to bind cells. Western blot, p24 core ELISA, and reverse transcription assays indicated that virions remained intact after treatment with beta-cyclodextrin at concentrations that abolished infectivity. Electron microscopy revealed that beta-cyclodextrin-treated HIV had a morphology very similar to that of untreated virus. R18 fluorescence dequenching studies showed that beta-cyclodextrin-treated HIV did not fuse to the membrane of susceptible cells. Dequenching was restored by replenishing virion-associated cholesterol. The results indicate that cholesterol in HIV particles is strictly required for fusion and infectivity. These observations in combination with those of past studies indicate beta-cyclodextrin to be an excellent candidate for use as a chemical barrier for AIDS prophylaxis. |
| Lipid rafts exist as stable cholesterol-independent microdomains in the brush border membrane of enterocytes Hansen, G. H., L. Immerdal, et al. (2001), J Biol Chem 276(34): 32338-44. Abstract: Glycosphingolipid/cholesterol-rich membranes ("rafts")can be isolated from many types of cells, but their existence as stable microdomains in the cell membrane has been elusive. Addressing this problem, we studied the distribution of galectin-4, a raft marker, and lactase, a protein excluded from rafts, on microvillar vesicles from the enterocyte brush border membrane. Magnetic beads coated with either anti-galectin-4 or anti-lactase antibodies were used for immunoisolation of vesicles followed by double immunogold labeling of the two proteins. A morphometric analysis revealed subpopulations of raft-rich and raft-poor vesicles by the following criteria: 1) the lactase/galectin-4 labeling ratio/vesicle captured by the anti-lactase beads was significantly higher (p < or = 0.01) than that of vesicles captured by anti-galectin-4 beads, 2) subpopulations of vesicles labeled by only one of the two antibodies were preferentially captured by beads coated with the respective antibody (p < or = 0.01), 3) the average diameter of "galectin-4 positive only" vesicles was smaller than that of vesicles labeled for lactase. Surprisingly, pretreatment with methyl-beta-cyclodextrin, which removed >70% of microvillar cholesterol, did not affect the microdomain localization of galectin-4. We conclude that stable, cholesterol-independent raft microdomains exist in the enterocyte brush border. |
| Lipid research. Possible new way to lower cholesterol Ferber, D. (2000), Science 289(5484): 1446-7. |
| Lipid responses to plant-sterol-enriched reduced-fat spreads incorporated into a National Cholesterol Education Program Step I diet Maki, K. C., M. H. Davidson, et al. (2001), Am J Clin Nutr 74(1): 33-43. Abstract: BACKGROUND: Plant sterol esters reduce cholesterol absorption and lower circulating blood cholesterol concentrations when incorporated into the habitual diet. OBJECTIVE: This randomized, double-blind, 3-group parallel, controlled study evaluated the influence of esterified plant sterols on serum lipid concentrations in adults with mild-to-moderate primary hypercholesterolemia. DESIGN: Subjects incorporated a conventional 50%-fat spread into a National Cholesterol Education Program Step I diet for a 4-wk lead-in period, followed by a 5-wk intervention period of the diet plus either a control reduced-fat spread (40% fat; n = 92) or a reduced-fat spread enriched with plant sterol esters to achieve intakes of 1.1 g/d (n = 92; low-sterol group) or 2.2 g/d (n = 40; high-sterol group). RESULTS: Subjects in the low- and high-sterol groups who consumed > or = 80% of the scheduled servings (per-protocol analyses) had total cholesterol values that were 5.2% and 6.6% lower, LDL-cholesterol values that were 7.6% and 8.1% lower, apolipoprotein B values that were 6.2% and 8.4% lower, and ratios of total to HDL cholesterol that were 5.9% and 8.1% lower, respectively, than values for the control group (P < 0.001 for all). Additionally, triacylglycerol concentrations decreased by 10.4% in the high-sterol group. Serum concentrations of fat-soluble vitamins and carotenoids were generally within reference ranges at baseline and postintervention. Serum plant sterol concentrations increased from baseline (0.48% of total sterol by wt) to 0.64% and 0.71% by wt for the low- and high-sterol groups, respectively (P < 0.05 compared with control). CONCLUSION: A reduced-fat spread containing plant sterol esters incorporated into a low-fat diet is a beneficial adjunct in the dietary management of hypercholesterolemia. |