| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Spreads enriched with plant sterols, either esterified 4,4-dimethylsterols or free 4-desmethylsterols, and plasma total- and LDL-cholesterol concentrations Sierksma, A., J. A. Weststrate, et al. (1999), Br J Nutr 82(4): 273-82. Abstract: In a 9-week study seventy-six healthy adult volunteers with an average age of 44 (SD 11) years, with baseline plasma total cholesterol levels below 8 mmol/l, received in a balanced, double-blind, crossover design, a total of three different table spreads for personal use. Two spreads were fortified either with free (non-esterified) vegetable-oil sterols, mainly from soyabean oil (31 g sterol equivalents/kg; 0.8 g/d) or sheanut-oil sterols (133 g sterol equivalents/kg; 3.3 g/d). One spread was not fortified (control). Average intake of spread was 25 g/d for 3 weeks. None of the spreads induced changes in blood clinical chemistry or haematology. Plasma total- and LDL-cholesterol concentrations were statistically significantly reduced by 3.8% and 6% (both 0.19 mmol/l) respectively, for the spread enriched with free soyabean-oil sterols compared with the control spread. The spread enriched with sheanut-oil sterols did not lower plasma total- and LDL-cholesterol levels. None of the plant-sterol-enriched spreads affected plasma HDL-cholesterol concentrations. Plasma-lipid-standardized concentrations of alpha- plus beta-carotene were not statistically significantly affected by the soyabean-oil sterol spread in contrast to lipid-standardized plasma lycopene levels which showed a statistically significant decrease (9.5%). These findings indicate that a daily intake of free soyabean-oil sterols as low as 0.8 g added to a spread is effective in lowering blood total- and LDL-cholesterol levels with limited effects on blood carotenoid levels. The lowering in total- and LDL-cholesterol blood levels due to consumption of the vegetable-oil-sterol-enriched spread may be helpful in reducing the risk of CHD for the population. |
| Spreads enriched with three different levels of vegetable oil sterols and the degree of cholesterol lowering in normocholesterolaemic and mildly hypercholesterolaemic subjects Hendriks, H. F., J. A. Weststrate, et al. (1999), Eur J Clin Nutr 53(4): 319-27. Abstract: OBJECTIVE: To investigate the dose-response relationship between cholesterol lowering and three different, relatively low intake levels of plant sterols (0.83, 1.61, 3.24 g/d) from spreads. To investigate the effects on lipid-soluble (pro)vitamins. DESIGN: A randomized double-blind placebo controlled balanced incomplete Latin square design using five spreads and four periods. The five study spreads included butter, a commercially available spread and three experimental spreads fortified with three different concentrations of plant sterols. SUBJECTS: One hundred apparently healthy normocholesterolaemic and mildly hypercholesterolaemic volunteers participated. INTERVENTIONS: Each subject consumed four spreads, each for a period of 3.5 week. RESULTS: Compared to the control spread, total cholesterol decreased by 0.26 (CI: 0.15-0.36), 0.31 (CI: 0.20-0.41) and 0.35 (CI: 0.25-0.46) mmol/L, for daily consumption of 0.83, 1.61 and 3.24 g plant sterols, respectively. For LDL-cholesterol these decreases were 0.20 (CI: 0.10-0.31), 0.26 (CI: 0.15-0.36) and 0.30 (CI: 0.20-0.41). Decreases in the LDL/HDL ratio were 0.13 (CI: 0.04-0.22), 0.16 (CI: 0.07-0.24) and 0.16 (CI: 0.07-0.24) units, respectively. Differences in cholesterol reductions between the plant sterol doses consumed were not statistically significant. Plasma vitamin K1 and 25-OH-vitamin D and lipid standardized plasma lycopene and alpha-tocopherol were not affected by consumption of plant sterol enriched spreads, but lipid standardized plasma (alpha + beta)-carotene concentrations were decreased by about 11 and 19% by daily consumption of 0.83 and 3.24 g plant sterols in spread, respectively. CONCLUSIONS: The three relatively low dosages of plant sterols had a significant cholesterol lowering effect ranging from 4.9-6.8%, 6.7-9.9% and 6.5-7.9%, for total, LDL-cholesterol and the LDL/HDL cholesterol ratio, respectively, without substantially affecting lipid soluble (pro)vitamins. No significant differences in cholesterol lowering effect between the three dosages of plant sterols could be detected. This study would support that consumption of about 1.6 g of plant sterols per day will beneficially affect plasma cholesterol concentrations without seriously affecting plasma carotenoid concentrations. |
| Spurious elevation of serum high-density lipoprotein cholesterol in patients with cholestatic liver diseases Chiba, H., T. Osaka, et al. (1991), Biochem Med Metab Biol 46(3): 329-43. Abstract: Strikingly discrepant values were obtained by two commercial precipitating reagents for serum HDL cholesterol determination in three patients with cholestatic liver diseases (two patients with primary biliary cirrhosis and one patient with chronic hepatitis). An abnormal alpha 2-migrating lipoprotein (slow alpha-lipoprotein) was observed in agarose gel electrophoresis for each serum. The slow alpha-lipoprotein was partly recovered in the supernatant by precipitation with polyethylene glycol, and was completely precipitated with a polyanion-containing reagent, which well explains the discrepancy. The slow alpha-lipoprotein isolated from one of the cases is notable for (1) having an intermediate particle size between normal LDL and normal HDL, (2) containing apo E as the major apolipoprotein, and (3) being enriched with cholesterol (esterified and free) and phospholipid. Cholesterol accumulation was also found in another HDL subclass, alpha 1-migrating HDL. A severe impediment in the clearance of cholesterol-loaded HDL particles from plasma was implied. Electrophoresis of serum lipoproteins and/or the measurement of serum apo E concentrations are necessary to avoid an erroneous estimation of HDL cholesterol in patients with hepatobiliary diseases. |
| Squalene does not exhibit a chemopreventive activity and increases plasma cholesterol in a Wistar rat hepatocarcinogenesis model Scolastici, C., T. P. Ong, et al. (2004), Nutr Cancer 50(1): 101-9. Abstract: The eventual chemopreventive effect of squalene (SQ), a triterpene present in olive oil, was evaluated when administered to Wistar rats during a period comprising the initiation and selection/promotion of the "resistant hepatocyte" (RH) model of hepatocarcinogenesis. During 8 consecutive wk, animals received by gavage SQ (100 or 150 mg/100 g body weight) dissolved in corn oil (CO) daily. Animals treated with only CO and submitted to the RH model were used as controls. Treatments with SQ did not result in inhibition of macroscopically visible hepatocyte nodules (P > 0.05) or of hepatic placental glutathione S-transferase- positive preneoplastic lesions (PNL; P > 0.05). Hepatic cell proliferation and apoptosis indexes were not different (P > 0.05) among the different experimental groups, both regarding PNL and surrounding normal tissue areas. There were no significant differences (P > 0.05) among comets presented by rats treated with the two SQ doses or with CO. On the other hand, SQ increased total plasma cholesterol levels when administered at both doses (P < 0.05). This indicates that the isoprenoid was absorbed. Thus, SQ did not present chemopreventive activity during hepatocarcinogenesis and had a hypercholesterolemic effect, suggesting caution when considering its use in chemoprevention of cancer. |
| Squalene epoxidase: another rate limiting enzyme in cholesterol biosynthesis Sakakibara, J. and T. Ono (1994), Tanpakushitsu Kakusan Koso 39(9): 1508-17. |
| Squalestatin 1, a potent inhibitor of squalene synthase, which lowers serum cholesterol in vivo Baxter, A., B. J. Fitzgerald, et al. (1992), J Biol Chem 267(17): 11705-8. Abstract: Squalestatin 1 is a member of a novel family of fermentation products isolated from a previously unknown Phoma species (Coelomycetes). Squalestatin 1 is a potent, selective inhibitor of squalene synthase, a key enzyme in cholesterol biosynthesis; in vitro, 50% inhibition of enzyme activity is observed at a concentration of 12 +/- 5 nM (range of 4-22 nM). Squalestatin 1 inhibits cholesterol biosynthesis from 14Cacetate by isolated rat hepatocytes (50% inhibition at 39 nM) and by rat liver in vivo. In marmosets, a species with a lipoprotein profile similar to that of man, squalestatin 1 lowers serum cholesterol by up to 75%. This compound will allow further investigation of the control of the sterol biosynthesis pathway and could also lead to the development of new therapies for elevated serum cholesterol. |
| SR-12813 lowers plasma cholesterol in beagle dogs by decreasing cholesterol biosynthesis Berkhout, T. A., H. M. Simon, et al. (1997), Atherosclerosis 133(2): 203-12. Abstract: SR-12813 inhibits cholesterol biosynthesis in Hep G2 cells via an enhanced degradation of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Here we also show that SR-12813 inhibits cholesterol biosynthesis in vivo. A sterol balance study was performed in normolipemic beagle dogs. The dogs were given SR-12813 orally at dosages of 10 and 25 mg/kg/day for a period of 9 days. After 7 days plasma cholesterol was decreased by 15% in the 10 mg/kg/day group and by 19% in the 25 mg/kg/day group. Using a dual isotope technique no effects on intestinal cholesterol absorption were observed. The sterol balance indicated that endogenous synthesis of cholesterol was reduced by 23% in the 10 mg/kg/day group and by 37% in the 25 mg/kg/day group. Plasma lathosterol-cholesterol levels in dogs treated with 25 mg/kg/day SR-12813 were reduced by 56%, confirming a reduction of the cholesterol biosynthesis. Treatment with SR-12813 or the HMG-CoA reductase inhibitor lovastatin resulted in a large decrease in low density lipoprotein (LDL) cholesterol. It is concluded that SR-12813 reduces cholesterol biosynthesis in the dog model which results in a decrease of bile acid excretion, cholesterol excretion and plasma cholesterol level. The in vivo profile of SR-12813 is very similar to that of direct HMG-CoA reductase inhibitors, although the mode of action of the compound is unique. |
| SR-BI- and ABCA1-mediated cholesterol efflux to serum from patients with Alagille syndrome Yancey, P. G., B. F. Asztalos, et al. (2004), J Lipid Res 45(9): 1724-32. Abstract: Alagille syndrome is associated with bile duct paucity resulting in liver disease. Patients can be divided into mildly and severely icteric groups, with both groups having altered lipoproteins. The incidence of ischemic heart disease is rare in severely cholestatic children despite increased total cholesterol and decreased high density lipoprotein cholesterol (HDL-C). The present studies examine the impact of altered lipid and lipoproteins on scavenger receptor class B type I (SR-BI)- and ABCA1-mediated efflux to serum from both groups. Efflux was compared with serum from 29 patients (15 with normal plasma cholesteryl ester, 14 with low cholesteryl ester). Efflux via SR-BI and ABCA1 was studied using cell systems having either low or high expression levels of these receptors. SR-BI efflux was lower (P = 0.04) with serum from severely icteric patients (3.9 +/- 1.4%) compared with serum from mildly icteric patients (5.1 +/- 1.4%) and was positively correlated with HDL-C and its apolipoproteins. SR-BI-mediated efflux was not correlated with any particular mature HDL but was negatively correlated with small lipid-poor prebeta-1 HDL. Consistent with severely icteric patients having high prebeta-1 HDL levels, the ABCA1 efflux was significantly higher with their serum (4.8 +/- 2.2%) compared with serum from mildly icteric patients (2.0 +/- 0.6%) and was positively correlated with prebeta-1 HDL. These studies demonstrated that prebeta-1 HDL is the preferred acceptor for ABCA1 efflux, whereas many particles mediate SR-BI efflux. |
| SR-BI and cholesterol uptake into steroidogenic cells Connelly, M. A. and D. L. Williams (2003), Trends Endocrinol Metab 14(10): 467-72. Abstract: Scavenger receptor class B, type I (SR-BI) is a receptor for high-density lipoprotein (HDL) that mediates cellular uptake of HDL cholesteryl ester (HDL CE) and is the major route for cholesterol delivery to the steroidogenic pathway. SR-BI is localized in specialized microvillar channels in the plasma membrane that retain HDL and are sites of selective uptake of HDL CE. The formation of microvillar channels in the adrenal gland requires SR-BI and is regulated by adrenocorticotropin hormone. SR-BI-mediated uptake of HDL CE is a two-step process that requires high-affinity binding of HDL followed by transfer of CE to the membrane. CE uptake is followed by hydrolysis to free cholesterol by a neutral CE hydrolase. In this review, we describe new information on the mechanism of transfer of cholesterol from plasma HDL to the steroidogenic pathway in endocrine cells. |
| SREBP cleavage-activating protein (SCAP) is required for increased lipid synthesis in liver induced by cholesterol deprivation and insulin elevation Matsuda, M., B. S. Korn, et al. (2001), Genes Dev 15(10): 1206-16. Abstract: In liver, the synthesis of cholesterol and fatty acids increases in response to cholesterol deprivation and insulin elevation, respectively. This regulatory mechanism underlies the adaptation to cholesterol synthesis inhibitors (statins) and high calorie diets (insulin). In nonhepatic cells, lipid synthesis is controlled by sterol regulatory element-binding proteins (SREBPs), membrane-bound transcription factors whose active domains are released proteolytically to enter the nucleus and activate genes involved in the synthesis and uptake of cholesterol and fatty acids. SCAP (SREBP cleavage-activating protein) is a sterol-regulated escort protein that transports SREBPs from their site of synthesis in the endoplasmic reticulum to their site of cleavage in the Golgi. Here, we produced a conditional deficiency of SCAP in mouse liver by genomic recombination mediated by inducible Cre recombinase. SCAP-deficient mice showed an 80% reduction in basal rates of cholesterol and fatty acid synthesis in liver, owing to decreases in mRNAs encoding multiple biosynthetic enzymes. Moreover, these mRNAs failed to increase normally in response to cholesterol deprivation produced by a cholesterol synthesis inhibitor and to insulin elevation produced by a fasting-refeeding protocol. These data provide in vivo evidence that SCAP and the SREBPs are required for hepatic lipid synthesis under basal and adaptive conditions. |
| SREBP controls cholesterol homeostasis Sato, R. and J. Sakai (2004), Seikagaku 76(6): 503-8. |
| SREBP2 and cholesterol metabolism Sato, R. (2001), Nippon Rinsho 59 Suppl 2: 264-9. |
| SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver Horton, J. D., J. L. Goldstein, et al. (2002), J Clin Invest 109(9): 1125-31. |
| SstI APO AI-CIII DNA polymorphism associated with lower levels of HDL cholesterol in a young population from south of Italy De Lorenzo, F., A. Monticelli, et al. (1993), Aust N Z J Med 23(6): 711-2. |
| Stability of cholesterol gall stones after 165 years of burial Wu, A. H. and N. F. Bellantoni (2003), J Forensic Sci 48(3): 633-4. Abstract: A woman who died in 1837 was exhumed for the purposes of moving the grave to another location. During the excavation, small white deposits of stone were uncovered in the right abdominal region, inferior to the rib cage and superior to the ilium blade. These stones were analyzed for cholesterol, bilirubin, and calcium following solubilization using methyl tert-butyl ether as a solvent. The results of these clinical chemistry analyses showed that these stones consisted primarily of cholesterol. Under these particular soil conditions encountered in this case, cholesterol gall stones are stable for at least 165 years. |
| Stability of mixed micellar systems made by solubilizing phosphatidylcholine-cholesterol vesicles by bile salts Lichtenberg, D., S. Ragimova, et al. (1990), Hepatology 12(3 Pt 2): 149S-153S; discussion 153S-154S. Abstract: Complete solubilization of phosphatidylcholine and cholesterol by bile salts in the form of stable mixed micelles requires that the effective ratio of bile salt/lipids in the mixed micelles (Re = (bile salt - critical micellar concentration)/(phosphatidylcholine + cholesterol) will exceed a critical value. This equilibrium solubilizing ratio is an increasing function of the cholesterol/phosphatidylcholine ratio. In contrast, the concentration of sodium cholate required for solubilization of vesicles made of phosphatidylcholine and cholesterol does not increase by increasing the cholesterol/phosphatidylcholine ratio. Consequently, the latter solubilization procedure yields metastable mixed micelles whenever the cholate concentration is higher than that required for vesicle solubilization but lower than that needed for establishing a micellar equilibrium. These metastable mixed micelles undergo partial revesiculation to form cholesterol-rich vesicles that subsequently aggregate. Cholesterol crystallization appears to occur through its reorganization within these aggregated vesicles. The overall rate of the above series of processes increases sharply with the total lipid concentration and with the cholesterol/phosphatidylcholine ratio. The dependence of the rate on the effective ratio of bile salts/lipids is very complex: at any given ratio of cholesterol/phosphatidylcholine within the range of 0.3 to 0.5, increasing the cholesterol/phosphatidylcholine ratio requires higher cholate concentrations for the formation of stable mixed micelles (higher equilibrium solubilizing ratio). On the other hand, the metastable mixed micellar larsystems are long-lived whenever the effective ratio of cholate/lipids is lower than a critical value.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Stabilization of caveolin-1 by cellular cholesterol and scavenger receptor class B type I Frank, P. G., Y. L. Marcel, et al. (2002), Biochemistry 41(39): 11931-40. Abstract: Caveolae are 50-100 nm plasma membrane invaginations, which function in cell signaling, in transcytosis, and in regulating cellular cholesterol homeostasis. These subcompartments of the plasma membrane are characterized by the presence of caveolin proteins. Recent studies have indicated that caveolae may be involved in the regulation of cellular cholesterol efflux to high-density lipoproteins (HDL), as well as selective cholesteryl ester uptake mediated by scavenger receptor class B type I (SR-BI). In the present studies, we show that caveolin-1 expression in HEK-293T cells has no effect on SR-BI-mediated cellular cholesterol efflux to reconstituted HDL. However, SR-BI-mediated selective cholesteryl ester uptake is significantly inhibited by caveolin-1. Interestingly, we also found that SR-BI, but not CD36, can induce the dramatic stabilization of the caveolin-1 protein, independently of its transcriptional control. On the other hand, caveolin-1 has little effect on SR-BI stability, but clearly increases CD36 stability. Since SR-BI expression has been shown to increase cellular cholesterol levels, we next examined the effect of cholesterol itself on caveolin-1 stabilization and localization. When cells were loaded with cholesterol, we observed the dramatic stabilization of caveolin-1 with significant clustering of caveolin-1 at the cell surface. In addition, a palmitoylation-deficient caveolin-1 mutant was still responsive to cholesterol-induced stabilization, indicating that palmitoylation of caveolin-1 is not required for the cholesterol-induced stabilization of caveolin-1. These results suggest an important role for cholesterol and SR-BI in the regulation of caveolin functioning, especially in cell types such as endothelial cells and macrophages, which can be dramatically affected by changes in their cholesterol content during the development of atherosclerosis. |
| Stable isotopes and mass isotopomer study of fatty acid and cholesterol synthesis. A review of the MIDA approach Lee, W. N. (1996), Adv Exp Med Biol 399: 95-114. |
| Stably transfected ABCA1 antisense cell line has decreased ABCA1 mRNA and cAMP-induced cholesterol efflux to apolipoprotein AI and HDL Zheng, P., A. Horwitz, et al. (2001), Biochim Biophys Acta 1534(2-3): 121-8. Abstract: Using a sensitive real time fluorescent PCR assay, ABCA1 mRNA levels were induced by approximately 50-70-fold following 8Br-cAMP treatment of the RAW264 murine macrophage cell line, concomitant with the induction of cholesterol efflux to apoAI and HDL. A stably transfected ABCA1 antisense cDNA cell line was created, which led to approximately 50-70% reductions in ABCA1 mRNA levels in basal and 8Br-cAMP-treated cells, and diminished to the same extent the 8Br-cAMP-mediated efflux of cholesterol to apolipoprotein AI and HDL. These data demonstrate that ABCA1 is necessary for the cAMP-induced lipid efflux to both apoAI and HDL. |
| Standardisation of cholesterol determination Boerma, G. J. (1990), J Clin Chem Clin Biochem 28(4): 259-60. |