| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Effect of probiotic supplementation on serum/yolk cholesterol and on egg shell thickness in layers Mohan, B., R. Kadirvel, et al. (1995), Br Poult Sci 36(5): 799-803. Abstract: 1. The effect of probiotic supplementation on egg production, on serum and yolk cholesterol and on egg shell thickness in 24 White Leghorn layers was studied from 28-38 weeks of age. 2. In 3 treatments the diet was supplemented with 0, 100 and 150 mg probiotic/kg food. 3. In the 100 mg probiotic group, egg production improved by 5%, and shell thickness improved slightly, with fewer thin-shelled eggs than in the control (8.6% compared to 18.6%). 4. The initial serum cholesterol concentration of 170.2 mg/dl in control birds remained similar throughout the 10-week experimental period, whereas in the 150 mg group the initial value of 176.5 mg/dl decreased to 114.3 mg by week 10. 5. Yolk cholesterol concentration was 14.69 mg in the control group and 11.28 and 11.37 mg/g in the 100 and 150 mg probiotic groups respectively. Overall mean total egg cholesterol was thus reduced by probiotic supplementation. |
| Effect of probucol in lecithin-cholesterol acyltransferase-deficient mice: inhibition of 2 independent cellular cholesterol-releasing pathways in vivo Tomimoto, S., M. Tsujita, et al. (2001), Arterioscler Thromb Vasc Biol 21(3): 394-400. Abstract: Cellular cholesterol release takes place by at least 2 distinct mechanisms: the lecithin-cholesterol acyltransferase (LCAT)-driven net efflux by cholesterol diffusion and the generation of high density lipoprotein (HDL) with cellular cholesterol and phospholipid on the cell-apolipoprotein interaction. Therefore, LCAT deficiency impairs the former pathway, and the latter can be inhibited by probucol, which interferes with the apolipoprotein-cell interaction. Hence, probucol was given to the LCAT-deficient mice in the attempt to suppress both of these pathways. The mice were fed low (0.2%) and high (1.2%) cholesterol diets containing 0.5% probucol for 2 weeks. LCAT deficiency and probucol markedly decreased plasma HDL, and the effects were synergistic. Tissue cholesterol content was lower in the adrenal glands and ovaries in the LCAT-deficient mice and in the probucol-treated mice, suggesting that HDL is a main cholesterol provider for these organs. It was also moderately decreased in the spleen of the low cholesterol-fed female mice and in the thyroid gland of the low cholesterol-fed male mice. On the other hand, the esterified cholesterol content in the liver was substantially increased by the probucol treatment with a high cholesterol diet in the LCAT-deficient mice but not in the wild-type mice. Among the groups, there was no significant difference in the tissue cholesterol levels in other organs, such as the liver, spleen, thymus, brain, erythrocytes, thyroid gland, testis, and aorta, resulting from either LCAT deficiency or probucol. Thus, the apolipoprotein-mediated mechanism plays a significant role in the export of cellular cholesterol in the liver, indicating that the liver is a major site of the HDL assembly. Otherwise, tissue cholesterol homeostasis can largely be maintained in mice even when the assembly of new HDL is inhibited by probucol in the absence of LCAT. Nonspecific diffusion of cholesterol perhaps adequately maintains the homeostasis in the experimental condition. |
| Effect of probucol on blood cholesterol and basal and lovastatin-induced 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in mice Gebhard, R. L., W. F. Prigge, et al. (1991), J Lab Clin Med 117(4): 299-304. Abstract: The drug probucol is known to reduce levels of blood cholesterol and to have antioxidant effects on lipoproteins that may alter their metabolism. While studying probucol feeding in mice, we observed that the drug lowered total hepatic, but not gut, 3-hydroxyl-3-methylglutaryl coenzyme A (HMG CoA) reductase activities during the diurnal cycle. Hepatic fatty acyl:cholesterol acyl transferase activity and cholesterol content were not measurably affected by probucol. Probucol also abolished the induction of HMG CoA reductase activity that resulted from feeding of lovastatin, when activity was measured in microsomes washed free of drugs. These effects are consistent with previous reports that probucol increases fractional clearance of lipoprotein cholesterol by the liver. The findings raise the possibility that some patients with hypercholesterolemia may benefit from combined therapy with lovastatin plus probucol. |
| Effect of progesterone on hydrophobic cell-associated proteoglycans bound to cholesterol sulfate in glandular epithelial cells of guinea-pig endometrium Nicollier, M., L. Beck, et al. (1994), Biochim Biophys Acta 1220(2): 125-31. Abstract: Sulfate incorporation was studied in subcultured glandular epithelial cells of guinea-pig endometrium untreated or treated with 10(-8) M 17 beta-estradiol alone or associated with various concentrations of progesterone. In the cells treated with progesterone in association with 17 beta-estradiol, the maximum of the 35S-labelled cell-associated macromolecules failed to bind with an anion-exchange resin (53% of total radioactivity) and had a hydrophobic character. This fraction was separated as an aggregate when the cells were extracted with 4 M guanidine-HCl, and separated as a single component in the presence of Triton X-100, suggesting that it aggregates with cellular lipid. The guanidine-extracted material contained 23.5% proteoglycans. However, the bulk of the radioactivity was in the sulfated lipids (68-75%), essentially represented by cholesterol sulfate. In the progesterone-treated cells, the amount of cholesterol sulfate was significantly higher than in 17 beta-estradiol-treated or untreated cells (1.35-1.5-fold). Thus, the effect of progesterone is located on a lipophilic proteoglycan associated with cholesterol sulfate. These results are discussed in relation to the preparation of the endometrium for embryo implantation. |
| Effect of propionate on fatty acid and cholesterol synthesis and on acetate metabolism in isolated rat hepatocytes Demigne, C., C. Morand, et al. (1995), Br J Nutr 74(2): 209-19. Abstract: In the present study the actual role of propionic acid in the control of fatty acid and cholesterol synthesis was investigated in isolated liver cells from fed rats maintained in the presence of near-physiological concentrations of glucose, glutamine and acetate. Using 3H2O for lipid labelling, propionate appears as an effective inhibitor of fatty acid synthesis and to a lesser extent of cholesterol synthesis, even at the lowest concentration used (0.6 mmol/l). Butyrate is a potent activator of both synthetic pathways, and the activating effect was not counteracted by propionate. Using 1-14Cacetate, it was observed that propionate at a moderate concentration, or 1 mmol oleate/l, are both very effective inhibitors of 14C incorporation into fatty acid and cholesterol. This incorporation was drastically inhibited when propionate and oleate were present together in the incubation medium. The net utilization of acetate by rat hepatocytes was impaired by propionate, in contrast to oleate. 1-14Cbutyrate was utilized at a high rate for fatty acid synthesis, but to a lesser extent for cholesterol synthesis; both processes were unaffected by propionate. Intracellular citrate concentration was not markedly depressed by propionate, whereas it was strongly elevated by butyrate. In conclusion, propionate may represent an effective inhibitor of lipid synthesis when acetate is a major source of acetyl-CoA, a situation which is encountered with diets rich in readily-fermentable fibres. The present findings also suggest that propionate may be effective at concentrations close to values measured in vivo in the portal vein. |
| Effect of protein kinase C on endoplasmic reticulum cholesterol Lange, Y., J. Ye, et al. (2002), Biochem Biophys Res Commun 290(1): 488-93. Abstract: Plasma membrane cholesterol both regulates and is regulated by effector proteins in the endoplasmic reticulum (ER) through a feedback system that is poorly understood. We now show that ER cholesterol varies over a fivefold range in response to experimental agents that act upon protein kinase C (PKC). Agents that activate Ca(2+)-dependent PKC phorbol-12-myristate-13-acetate (PMA) and bryostatin 1 increased the level of ER cholesterol; inhibitors such as staurosporine and calphostin C decreased it. Rottlerin, a selective inhibitor of the PKC-delta isoform, also increased ER cholesterol. The esterification of plasma membrane cholesterol was altered by protein kinase C-directed agents in a corresponding fashion. Furthermore, the regulatory effect of plasma membrane cholesterol on the esterification of ER cholesterol was blocked by PKC-directed agents. These findings suggest that multiple protein kinase C isoforms participate in the regulation of ER cholesterol and therefore in cholesterol homeostasis. |
| Effect of psyllium hydrophilic mucilloid on serum cholesterol in the elderly Stewart, R. B., W. E. Hale, et al. (1991), Dig Dis Sci 36(3): 329-34. Abstract: The effect of psyllium hydrophilic mucilloid (PHM) when used as a laxative and/or stool softener on serum cholesterol concentrations was examined in 176 ambulatory elderly participants attending a health screening program. The change in one-year serum cholesterol concentration in subjects using PHM was compared with the change in cholesterol in 741 participants who did not report the use of PHM. Serum cholesterol concentration decreased by 0.073 mmol/liter (2.82 mg/dl) in the treatment group compared with a decrease of 0.036 mmol/liter (1.39 mg/dl) in the control group. After adjusting for confounding factors, excluding psyllium dose, by using a multiple regression model there was no significant difference in the change in serum cholesterol concentration (P = 0.935). PHM dosage information was available for 158 participants. After adjusting for baseline serum cholesterol and confounding factors using multiple regression analysis, it was found that the dose of PHM administered was significantly correlated with the change in serum cholesterol (P = 0.0120). For every 1-g increase in daily PHM dose there was a 0.022 mmol/liter (0.84 mg/dl) decrease in serum cholesterol concentration. |
| Effect of pulmonary surfactant protein A (SP-A) and calcium on the adsorption of cholesterol and film stability Yu, S. H. and F. Possmayer (1994), Biochim Biophys Acta 1211(3): 350-8. Abstract: The effect of exogenous cholesterol on the stability of surface films at 37 degrees C from various surfactants was studied with the pulsating bubble surfactometer. Addition of cholesterol (5%, w/w) to bovine lipid extract surfactant (bLES) or mixtures of dipalmitoylphosphatidylcholine/1-palmitoyl-2-oleoyl-phosphatidylglycerol /SP-B (7:3:1%) dispersed in 1.5 mM CaCl2/0.9% NaCl resulted in unstable surface films. Although 10% cholesterol only partially impaired the surface activity of bLES, it virtually abolished that of the reconstituted surfactant. The inhibitory effects of cholesterol were significantly repressed by SP-A (10%, w/w of lipid) and 3 mM CaCl2 or 5 mM CaCl2 without SP-A. Adsorption of cholesterol from various surfactants into the air/water interface was examined by measuring the surface radioactivity of 14Ccholesterol. Cholesterol alone dispersed in 1.5 mM CaCl2/0.9% NaCl could not adsorb to the interface, but it adsorbed readily when mixed with bLES. Cholesterol adsorption was markedly suppressed by SP-A in 3 mM CaCl2/0.9% NaCl or 5 mM CaCl2/0.9% NaCl without SP-A. Electron microscopy revealed striking ultrastructural differences between bLES/5% cholesterol/10% SP-A in 3 mM CaCl2/0.9% NaCl and bLES/5% cholesterol in 3 or 5 mM CaCl2/0.9% NaCl. The former exhibited large multilayer and small unilamellar vesicles, while the latter displayed condensed patches of aggregates. Adsorption studies showed aggregated patches adsorbed more rapidly than vesicles but attained lower equilibrium surface pressures. These results indicate SP-A and calcium limit the adsorption of surfactant cholesterol to the air-water interface. |
| Effect of pulsed magnetic fields on cholesterol and tryglyceride levels in rats study of field intensity and length of exposure Bellossi, A., V. Pouvreau-Quillien, et al. (1996), Z Naturforsch C 51(7-8): 603-6. Abstract: In a previous work a decrease in cholesterol and triglyceride plasma levels was observed in rats 24 hours after their exposure to a 12 Hz 6 mT pulsed magnetic field (PMF). This time, a study of intensity effects of a 12 Hz PMF for a sixty-minute exposure and of length of exposure for a 12 Hz 6 mT PMF took place. Non-linear effect-dose relationships were observed for the PMF intensity as well as for the length of exposure used. The highest decreases in cholesterol and triglyceride levels were obtained after to a sixty-minute exposure with 1.5 mT and 12 mT. |
| Effect of pulsed magnetic fields on triglyceride and cholesterol levels in plasma of rats Bellossi, A., V. Pouvreau-Quilien, et al. (1998), Panminerva Med 40(4): 276-9. Abstract: BACKGROUND: Liver is a crucial organ in metabolism. For instance liver is the main source of circulating lipoproteins. METHODS: In this paper cholesterol and triglyceride plasma levels were measured in male rats previously exposed to pulsed magnetic fields (PMF) used in therapy. Rats underwent a one-hour exposure to a 6 mT 12 Hz PMF. RESULTS: Twenty-four hours after the end of the exposure to the PMF the rats' livers were heavier, cholesterol and triglyceride plasma levels decreased. All these variations were significantly different according to a variance ratio test as was a rebound in triglyceride level 48 hours after the end of the exposure. Normal values were observed 48 and 96 hours after the end of exposure respectively for cholesterol and triglycerides. CONCLUSIONS: These alterations may be due to a reversible accumulation of either triglycerides or of their precursors in liver following acute exposure to a 12 Hz PMF. |
| Effect of pure and oxidized cholesterol-rich diets on some biochemical parameters in rats Al Kanhal, M. A., F. Ahmad, et al. (2002), Int J Food Sci Nutr 53(5): 381-8. Abstract: The present study was undertaken to evaluate the peroxidative damage and hypercholesterolemia induced in male Wistar albino rats by diets enriched either with 1% oxidized cholesterol (OC) (containing 49.8% of cholesterol oxidation products) or pure cholesterol (PC). The damage caused by the OC diet was revealed by a significant rise in red blood cell hemolysis, increased tissue lipid peroxidation and elevated aspartate amino transferase activity as compared with control and PC diets. Liver glutathione-S-transferase activity was decreased by both OC (P < 0.01) and PC (P < 0.05) diets, but glutathione was observed to be decreased only by the OC diet. Plasma triacylglycerol and cholesterol were increased significantly with both the OC and PC diets. Liver cholesterol and triacylglycerol were increased significantly with the OC diet only. These results indicate that the oxidative damage caused by the OC diet is much more pronounced than that caused by the PC diet. |
| Effect of purified pre-beta 1 HDL on efflux of 3H-cholesterol loaded in human smooth muscle cells Wu, X. W., L. C. Yang, et al. (2004), Sichuan Da Xue Xue Bao Yi Xue Ban 35(1): 18-20. Abstract: OBJECTIVE: To compare the effects of different HDL subclasses on the efflux of 3H-cholesterol loaded human smooth muscle cells (SMCS). METHODS: 3H-cholesterol loaded human SMCS were incubated with purified pre-beta 1 HDL, alpha-HDL and apoE-deficient HDL3 respectively. The cholesterol effluxing capacity and incubating time of different HDL subclasses were detected, and were analysed by double-reciprocal mapping. RESULTS: It was found that the value of Emax of pre-beta 1 HDL is higher than that of alpha-HDL and apoE-deficient HDL3 (P < 0.01), and the value of Ke of pre-beta 1 HDL is lower than that of alpha-HDL and apoE-deficient HDL3 (P < 0.01). CONCLUSION: The results showed the effluxing capacity and efficiency of pre-beta 1 HDL were greater than those of alpha-HDL and apoE-deficient HDL3, thus suggesting that pre-beta 1 HDL is a more efficient acceptor of cell-derived 3H-cholesterol. |
| Effect of raloxifene and hormone therapy on serum markers of brain and whole-body cholesterol metabolism in postmenopausal women Vogelvang, T. E., V. Mijatovic, et al. (2005), Maturitas 50(4): 312-20. Abstract: OBJECTIVE: To compare the 2-year effects of raloxifene (Rlx) with oral postmenopausal hormone therapy (HT) on serum markers of brain and whole-body cholesterol metabolism. METHODS: In a randomized, double-blind, placebo-controlled trial, 95 healthy, non-hysterectomized, early postmenopausal women received either daily Rlx 60 mg (n = 24), Rlx 150 mg (n = 23), HT (conjugated equine estrogens 0.625 mg/medroxyprogesterone acetate 2.5 mg; n = 24), or placebo (n = 24). Fasting blood samples were collected at baseline and after 6, 12, and 24 months of treatment for measurement of serum concentrations of cholesterol by means of gas-liquid chromatography; 24S-hydroxycholesterol (cerebrosterol), lathosterol, and the plant sterol campesterol by means of gas-liquid chromatography-mass spectrometry. The analyses were performed retrospectively from serum samples stored at -70 degrees C for 5 years. RESULTS: Twenty-four months of treatment with raloxifene 150 mg was associated with a significant reduction in serum cholesterol concentrations (-10%, P = 0.007). The ratio of 24S-hydroxycholesterol to cholesterol, a serum marker of brain cholesterol metabolism, showed a significant increase after 6 and 12 months with raloxifene 150 mg but not after 24 months (P = 0.001). The ratio of lathosterol to cholesterol, a marker of whole-body cholesterol synthesis, increased with raloxifene 60 mg (P = 0.163), raloxifene 150 mg (P < 0.001), as well as with HT (P = 0.005). The ratio of campesterol to cholesterol, a marker of cholesterol absorption rate, was significantly reduced with HT (P = 0.002). CONCLUSION: Two-year treatment with raloxifene or HT had no influence on brain cholesterol metabolism, while whole-body cholesterol synthesis, assessed by the ratio of lathosterol to cholesterol, increased during raloxifene and HT. |
| Effect of rat plasma high density lipoprotein with or without apolipoprotein E on the cholesterol uptake and on the induction of the corticosteroid biosynthetic pathway in newborn rat adrenocortical cell cultures Hammami, M., S. Meunier, et al. (1991), Biochim Biophys Acta 1094(2): 153-60. Abstract: High density lipoprotein (HDL) has been shown to induce the cellular accumulation of cholesterol esters and the biosynthetis of 21-hydroxysteroids (corticosteroids) newborn rat adrenocortical cells cultivated in serum-free medium. In order to identify the component(s) of HDL responsible for these effects, we investigated the ability of rat HDL subfractions and HDL with or without apolipoprotein E to deliver cholesterol to cells and to stimulate the steroid biosynthetic pathways in adrenal cultured cells. The total cholesterol uptake from HDL2 was greater than that observed with HDL rich in apolipoprotein E (HDL1 and HDLc). Furthermore, the increase of the ratio between 21-hydroxysteroids and reductive metabolites of progesterone was higher with HDL2 than with HDL1 or HDLc. The results of competitive studies between LDL and HDL subfractions indicate that adrenal cells take up cholesterol from HDL2 and LDL by separate mechanisms but that LDL and HDL containing apolipoprotein E share the same uptake processes. In experiments with various concentrations of HDLc or HDL without apolipoprotein E, the adrenal cells displayed a higher affinity for rat HDLc than for rat HDL without apolipoprotein E. However, HDL without apolipoprotein E produced a higher enhancement of the cholesterol cell content and was 3-fold more effective in stimulating 21-hydroxylated steroid production than rat HDLc. Although these findings suggest a participation of HDL with apolipoprotein E in the HDL interaction with rat adrenal cells, the predominant effect on these cells is devoluted to HDL containing mainly apolipoprotein A. |
| Effect of raw and cooked nopal (Opuntia ficus indica) ingestion on growth and profile of total cholesterol, lipoproteins, and blood glucose in rats Cardenas Medellin, M. L., S. O. Serna Saldivar, et al. (1998), Arch Latinoam Nutr 48(4): 316-23. Abstract: Two different concentrations (approx. 6 and 12%) and two presentations (raw and cooked) of dehydrated nopal were fed to laboratory rats and growth and serum total cholesterol, lipoprotein profile and glucose determined. Samples of raw and cooked nopal were chemically characterized for moisture, protein, ash, crude fiber, ether extract, total dietary fiber, reducing sugars, amino acids, minerals and gross energy. Cooking slightly affected some of the nutrients analyzed. After one month feeding, blood was withdrawn via intracardiac puncture and serum glucose, total cholesterol, HDL, LDL, and VLDL were determined. Rats fed 12% nopal had lower weight gains (P < 0.05) when compared with counterparts fed 6% nopal or the control diet. Consumption of nopal did not affect (P > 0.05) glucose, total cholesterol and HDL cholesterol levels. However, rats fed raw nopal at the 12% concentration level had a 34% reduction in LDL cholesterol levels; thus, it was concluded that raw nopal had a potentially beneficial effect for hypercholesterolemic individuals. |
| Effect of red mold rice supplements on serum and egg yolk cholesterol levels of laying hens Wang, J. J. and T. M. Pan (2003), J Agric Food Chem 51(16): 4824-9. Abstract: Monacolin K is a secondary metabolite of Monascus species and reduces cholesterol levels. This research focuses on the effect of adding red mold rice to hens' diet on cholesterol level in egg yolk and on cholesterol, triglyceride, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels in serum. Forty-eight Hy-line laying hens of 48 weeks of age were studied by dividing them into four groups. Except for the control group, the feed for three other groups contained 2.0, 5.0, and 8.0% red mold rice (monacolin K concentrations were 0.0145, 0.035, and 0.056%, respectively). The experiment lasted 6 weeks. During this period, egg weight and egg production were recorded every day, and cholesterol, triglyceride, HDL, and LDL in serum were measured weekly as well. The result showed that the cholesterol in eggs produced by experimental groups was lower than that of the control group (0%, 194.14 +/- 8.30; 2%, 167.17 +/- 4.34; 5%, 168.93 +/- 9.38; 8%, 183.02 +/- 7.63 mg/egg; p < 0.05), and the triglyceride (0%, 1494 +/- 178; 2%, 1280 +/- 174; 5%, 1189 +/- 248; 8%, 1381 +/- 218 mg/dL; p < 0.05) and LDL levels (0%, 36.81 +/- 5.53; 2%, 32.25 +/- 7.93; 5%, 30.06 +/- 4.39; 8%, 28.81 +/- 4.16 mg/dL; p < 0.05) were also significantly lowered in the experimental groups. However, the HDL level did not show significant change for either control or experimental groups (0%, 36.06 +/- 3.96; 2%, 36.25 +/- 5.39; 5%, 33.13 +/- 3.68; 8%, 31.44 +/- 4.29 mg/dL; p > 0.05). Besides, the addition of red mold rice also helps to inhibit production of malondialdehyde (MDA) in serum lipid oxidation (0%, 27.42 +/- 0.53; 2%, 25.62 +/- 0.76; 5%, 24.35 +/- 0.59; 8%, 23.63 +/- 0.48 microM; p < 0.05). |
| Effect of red wine on oxidative stress and hypercholesterolemia induced by feeding a high-cholesterol diet in rat Montilla, P., I. Espejo, et al. (2004), J Physiol Biochem 60(4): 259-64. Abstract: The effect of red wine on oxidative stress and hypercholesterolemia induced by feeding a high-cholesterol diet (supplemented with 1.65% of cholesterol (w/w) for 4 weeks) to female Wistar rats was examined. When red wine was simultaneously supplemented to high-cholesterol diet, total cholesterol, triglycerides, atherogenic index and lipid peroxidation products significantly decreased compared with the high-cholesterol diet alone, while GSH content and antioxidative enzymes activities were enhanced. In the hypercholesterolemic rat the excretion of fecal bile acids, as well as their plasma and hepatic concentrations were increased significantly. Administration of red wine enhanced these values, indicating an increase in the cholesterol degradation. These results suggest that red wine may have a protective effect against oxidative stress, hypercholesterolemia and atherogenic index induced by high-cholesterol diet. |
| Effect of reduced low-density lipoprotein receptor level on HepG2 cell cholesterol metabolism Izem, L., E. Rassart, et al. (1998), Biochem J 329 (Pt 1): 81-9. Abstract: Low-density lipoproteins (LDL) are taken up by both LDL receptor (LDLr)-dependent and -independent pathways. In order to determine the importance of these pathways in the activity of the various enzymes that are important in maintaining the cellular cholesterol level in hepatic cells, we created HepG2 cells expressing lower levels of LDLr. Thus HepG2 cells were transfected with a constitutive expression vector (pRc/CMV) containing a fragment of LDLr cDNA inserted in an antisense manner. Stable transformants were obtained that showed significant reductions of 42, 72 and 85% of LDLr protein levels compared with the control, as demonstrated by immunoblotting and confirmed by the LDL binding assay. The best inactivation was achieved with the construct containing the first 0.7 kb of LDLr cDNA. Incubating the different HepG2 cell subtypes with LDL showed similar association of apolipoprotein B (apo B) or cholesteryl esters from LDL with the cells, indicating that the LDLr deficiency did not significantly affect LDL uptake by the cell. However, apoB degradation was reduced significantly by 71-82% in the most LDLr-deficient HepG2 cells. We also found that 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCoA red) activity is significantly increased by 32-35% in HepG2 cells expressing very low levels of LDLr that also demonstrate a significant decrease of 20% in acyl-CoA:cholesterol acyltransferase (ACAT) activity. However, these effects are moderate compared with those observed when cells were incubated in lipoprotein-depleted medium, where a >900% increase in HMGCoA red activity and a loss of 60% of ACAT activity was observed. Thus, in HepG2 cells, different levels of LDLr affect LDL-apoB degradation, but have very little effect on LDL association, HMGCoA red and ACAT activities, revealing that LDLr is more important in the clearance of LDL-apoB than in HepG2 cell cholesterol homoeostasis, a role that should be attributable to both LDLr-dependent and -independent pathways. |
| Effect of reduction of plasma triglycerides with gemfibrozil on high-density-lipoprotein-cholesterol concentrations Rubins, H. B. and S. J. Robins (1992), J Intern Med 231(4): 421-6. Abstract: The aim of this study was to test the hypothesis that the plasma triglyceride (TG) concentration must be reduced below approximately 0.85-1.13 mmol l-1 (75-100 mg/dl-1) in order to achieve a substantial increase in plasma high-density-lipoprotein-cholesterol (HDL-C) levels. The study design consisted of a non-randomized clinical trial, which was conducted at an out-patient clinic at a university-affiliated VA Medical Center. The participants consisted of 55 ambulatory middle-aged men with a baseline fasting HDL-C concentration of less than or equal to 1.17 mmol l-1 (45 mg dl-1) and baseline TG in the range 1.13-5.6 mmol l-1 (100-500 mg dl-1). Subjects were treated with gemfibrozil, 600 mg twice a day for 3 months. Fasting plasma HDL-C, TG, low density lipoprotein-cholesterol, and total cholesterol were measured at 1-month intervals for 3 months. Subjects were divided into three groups on the basis of TG level achieved on therapy: Group I (n = 14), TG less than 0.85 mmol l-1 (75 mg dl-1); Group II (n = 20), TG 0.86-1.41 mmol l-1 (76-125 mg dl-1); Group III (n = 21), TG greater than 1.41 mmol l-1 (125 mg dl-1). The mean increase in HDL-C in Group I was 0.20 mmol l-1 (7.8 mg dl-1), a significantly (P = 0.0067) greater increase than was observed in the other two groups. There was no correlation between the magnitude of change in TG and the magnitude of change in HDL-C concentration in the group as a whole (Pearson's correlation coefficient, r = -0.06, P = 0.6). In conclusion, the increase in HDL-C levels observed with gemfibrozil therapy is associated with the absolute level of TG achieved by therapy. Substantial increases in HDL-C concentration might not be expected to occur consistently unless TG levels are reduced to values that are considered below the usually cited 'normal' range. |
| Effect of regulating cholesterol biosynthesis on breath isoprene excretion in men Stone, B. G., T. J. Besse, et al. (1993), Lipids 28(8): 705-8. Abstract: Isoprene is a normal constituent of human breath and may be derived from the cholesterol synthetic pathway. Acute and chronic lovastatin and a cholesterol-supplemented diet were used to determine whether a mechanistic link exists between isoprene and cholesterol biosynthesis in vivo in humans. The acute effects of lovastatin, a competitive inhibitor of the rate-limiting step of cholesterol biosynthesis, on breath isoprene excretion was determined by administering a single 20, 40 or 80 mg dose of this drug to five healthy male subjects at 8 p.m. and measuring their breath isoprene levels every 4 h for one 24 h cycle before and after treatment. When compared to the baseline cycle, all three doses of lovastatin significantly reduced breath isoprene levels at 6 and 10 h post-drug treatment. Chronic lovastatin therapy (40 mg b.i.d. for 6 wk) reduced 6 a.m. breath isoprene levels (time of maximum baseline value) by 27 +/- 9% (SEM) and cholesterol synthesis measured in freshly isolated mononuclear leukocytes (ML) by 12 +/- 6%. A cholesterol-supplemented diet (1070 mg, total) ingested for 6 wk reduced breath isoprene excretion and ML sterol synthesis by 16 +/- 5 and 19 +/- 4%, respectively. The parallel decreases in isoprene excretion and cholesterol synthesis caused by these pharmacologic and dietary means suggest that breath isoprene is derived from the cholesterol synthesis pathway. |