| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Cholesterol metabolism in ExHC (exogenous hypercholesterolemic) rats Imaizumi, K., A. Nagatomi, et al. (1992), Biochim Biophys Acta 1123(1): 101-9. Abstract: Exogenous hypercholesterolemic (ExHC) rats, that develop hypercholesterolemia for exogenous cholesterol, are an established strain Isolated from Sprague-Dawley (SD) rats by Imai and Matsumura ((1973) Atherosclerosis, 18, 59-64). The present study was carried out to clarify the cause of hyperresponsivity in ExHC rats to dietary cholesterol. As early as one day after feeding a high cholesterol diet (1%) serum cholesterol level was doubled in ExHC rats, while the level of hepatic cholesterol was two-thirds of SD rats. The elevation of serum cholesterol was mainly attributed to the d less than 1.006 g/ml fractions. Cholesterol feeding increased fecal bile acid excretion in both strains, but to a more greater extent in SD rats. Absorption of dietary cholesterol and synthesis of cholesterol in vivo were similar between the strains. The uptake of beta-very-low-density-lipoproteins (beta-VLDL) in vivo and the primary cultured hepatocytes was lower in ExHC rats, when a high-cholesterol diet was fed. Even without feeding of a high-cholesterol diet, preincubation with cholesterol-rich lipoproteins caused a lower association and degradation of beta-VLDL by the hepatocytes from ExHC rats. Incubation of hepatocytes with cholesterol-rich lipoproteins did not affect the secretion of 14Ccholesterol into the density less than 1.006 g/ml fraction, but suppressed the secretion into the medium density greater than 1.006 g/ml fractions. These results suggest that ExHC rats, as compared to SD rats, are defective of hepatic uptake and processing cholesterol to bile acids. |
| Cholesterol metabolism in familial hypertriglyceridemia: effects of obesity versus triglyceride level Duane, W. C. (1997), J Lab Clin Med 130(6): 635-42. Abstract: Excessive production of cholesterol has been associated with type IV hyperlipidemia, but the influence of the confounding variable of obesity has been difficult to ascertain. Moreover, cholesterol metabolism has not been systematically evaluated in patients with familial hypertriglyceridemia (FHT), one of the two major subsets of type IV patients. We used isotope dilution to measure cholesterol production, pools, and kinetic constants in 8 hypertriglyceridemic subjects, 6 of whom could be confidently classified as FHT. These were compared with measurements in 9 control subjects matched for sex, age, serum cholesterol, and body mass index (BMI). By t test, hypertriglyceridemic subjects did not differ from controls with respect to cholesterol production, size of readily or slowly miscible pools, or kinetic transfer coefficients. Results were the same whether controls were compared with all hypertriglyceridemic patients or only the 6 with definite FHT. By analysis of covariance (ANCOVA), serum triglyceride level was not a significant determinant of any parameter of cholesterol metabolism. However, BMI was a highly significant determinant of cholesterol production (p = 0.0001) and size of both readily and slowly miscible pools (p = 0.001 to 0.008). These data suggest that FHT per se is not associated with abnormalities of cholesterol metabolism but that an apparent association could result from the confounding variable of obesity. |
| Cholesterol metabolism in fibroblasts from rabbits resistant to diet-induced hypercholesterolemia Soma, M. R., J. D. Morrisett, et al. (1990), J Lipid Res 31(6): 985-94. Abstract: We have previously described a colony of New Zealand White rabbits that are resistant to hypercholesterolemia when fed a cholesterol-enriched diet. The present studies used skin fibroblasts obtained from normal and hypercholesterolemia-resistant rabbits to investigate cholesterol metabolism and lipid composition in vitro. The lipid compositions of the two cell lines after incubation in either fetal calf serum or lipoprotein-deficient serum were similar. The conversion of radiolabeled acetate into sterol and phospholipids was higher in resistant fibroblasts than in normal fibroblasts. In contrast, incorporation of radiolabeled oleic acid into cholesteryl ester was significantly lower in resistant fibroblasts than in normal cells. In parallel experiments, the 3-hydroxy-3-methylglutaryl coenzyme A reductase activity was higher and acyl-coenzyme A:cholesterol acyltransferase activity was lower in resistant cells compared to normal cells. Furthermore, binding, uptake, and degradation of normal rabbit 125I-labeled LDL (low density lipoproteins) were 30% higher in resistant than in normal fibroblasts. These observations are consistent with results from previous studies of cholesterol metabolism in the liver membranes of these rabbits. The results indicate that extrahepatic cells (such as fibroblasts) from the resistant rabbit exhibit the same altered cholesterol metabolism as that found in the hepatic tissues of these rabbits. These studies suggest that the resistant rabbit may provide an in vivo and in vitro system for studying the mechanisms by which some individuals of a species can minimize the effect of dietary cholesterol on the development of hypercholesterolemia and atherosclerosis. |
| Cholesterol metabolism in glomerular cells: effect of lipoproteins from nephrotic patients Wanner, C., A. Kramer-Guth, et al. (1996), Miner Electrolyte Metab 22(1-3): 39-46. Abstract: Although hyperlipidemia is a well recognized complication of the nephrotic syndrome, the precise metabolism of human lipoproteins by human glomerular cells and the effects of abnormalities in lipid and protein composition on this process have not been defined. This study examined the effects of apoB-100 containing low-density-lipoprotein (LDL) and apo B,E, containing intermediate-density lipoprotein (IDL), isolated from patients with the nephrotic syndrome (n = 6), on intracellular sterol synthesis and cholesterol esterification by human glomerular epithelial and mesangial cells. For comparison studies, human skin fibroblasts and Hep G2 cells were used. In the patients, serum LDL cholesterol level was increased threefold and IDL tenfold as compared to healthy subjects. LDL of nephrotic patients showed no differences in lipid/protein composition as compared to control LDL but IDL contained 58% more cholesterol than IDL from healthy controls. Therefore, nephrotic and control LDL showed identical inhibition of intracellular sterol synthesis and similar cholesteryl ester formation in all the four cell types. In contrast, cholesterol-rich IDL of nephrotic patients suppressed intracellular sterol synthesis more effectively than control IDL. The cholesterol esterification rate of IDL from patients was enhanced three fold on average as compared to control IDL. The various cell types differed in their rate of LDL esterification. The data indicate that the enhanced inhibition of intracellular sterol synthesis and cholesterol esterification by apo E-containing cholesterol-ester-rich IDL, which accumulate in nephrotic patients, may render these lipoproteins possible candidates for glomerular lipid deposition and progressive renal injury. |
| Cholesterol metabolism in human gallbladder mucosa: relationship to cholesterol gallstone disease and effects of chenodeoxycholic acid and ursodeoxycholic acid treatment Sahlin, S., J. Ahlberg, et al. (1992), Hepatology 16(2): 320-6. Abstract: The objective of this study was to investigate cholesterol metabolism in human gallbladder mucosa, especially in relation to hepatic cholesterol metabolism, gallstone disease and treatment with bile acids. Gallbladder mucosa and liver tissue samples were collected in 44 patients undergoing cholecystectomy; 30 had cholesterol gallstones and the rest were stone free. Ten of the gallstone patients were treated with chenodeoxycholic acid and eight received ursodeoxycholic acid, with a daily dose of 15 mg/kg body wt, for 3 wk before surgery. The 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, governing cholesterol synthesis, was considerably lower in the gallbladder mucosa than in liver tissue (28 +/- 6 and 120 +/- 40 pmol/min/mg protein). The acyl coenzyme A:acyltransferase activity in the gallbladder mucosa catalyzing the esterification of cholesterol was, on the other hand, several times higher than corresponding activity in the liver (92 +/- 23 and 11 +/- 2 pmol/min/mg protein). In the presence of exogenous cholesterol, the acyl coenzyme A:acyltransferase activity increased about twofold in the gallbladder mucosa. The acyl coenzyme A:acyltransferase activity of the gallbladder mucosa from untreated gallstone patients was not stimulated further by the addition of exogenous cholesterol. Otherwise, there were no significant differences in acyl coenzyme A:acyltransferase and 3-hydroxy-3-methylglutaryl coenzyme A reductase activities in the gallbladder mucosa of gallstone patients compared with gallstone-free controls. Treatment with chenodeoxycholic and ursodeoxycholic acids did not affect the 3-hydroxy-3-methylglutaryl coenzyme A reductase activity of the gallbladder mucosa but reduced the acyl coenzyme A:acyltransferase activity by 60% to 65%.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Cholesterol metabolism in human umbilical arterial endothelial cells cultured in low magnesium media Kummerow, F. A., M. Mahfouz, et al. (1997), Magnes Res 10(4): 355-60. Abstract: Epidemiological and experimental studies have shown that magnesium is closely related to regulation of lipid metabolism, membrane structure and permeability, ion migration through cellular membranes, endocrine hormone and platelet function. The cause of atherosclerosis induced by magnesium deficiency has been suggested to be due to abnormal lipid metabolism, lipid peroxidation, a decrease of prostacycline produced by endothelial cells, and an increase of platelet aggregation. We found that the plasma from cardiac catheterized patients suffering from chest pains contained higher levels of oxysterols than age and sex matched patients free of chest pain. Studies with cultured arterial cells in media deficient in magnesium or containing oxysterols indicated that both magnesium and oxysterols have an important role in lipid metabolism in patients with coronary heart disease. |
| Cholesterol metabolism in human umbilical arterial endothelial cells cultured in low magnesium media Zhou, Q. and F. A. Kummerow (1996), Magnes Res 9(4): 273-80. Abstract: To study the time- and dose-dependent effects of low magnesium on free H3cholesterol uptake, H3mevalonolactone incorporation into cholesterol, and both of which labelled precursors and H3oleic acid incorporations into cholesteryl esters, cultured human umbilical arterial endothelial cells were exposed to experimental media containing decreasing magnesium concentrations at 94, 188, 376 and 564 microM until 48 h. A level of magnesium at 949 microM was used as a control. The results showed that reduced magnesium in the cultured medium led to a decrease in H3cholesterol, uptake, an inhibition of the incorporation of H3mevalonolactone into cholesterol and a stimulation of the incorporation of H3cholesterol, H3mevalonolactone and H3oleic acid into cholesteryl esters, but the time- and dose-dependent effects of magnesium deficiency were not significant. We suggest that reduced cholesterol uptake and synthesis might contribute to hypercholesterolaemia under a condition of magnesium deficiency, and that enhanced cholesterol esterification might be explained by a stimulated activity of acyl-Coenzyme A: cholesterol O-acyltransferase (ACAT). |
| Cholesterol metabolism in hypercholesterolemia-resistant rabbits Loose-Mitchell, D. S., J. A. Poorman, et al. (1991), Atherosclerosis 87(2-3): 169-81. Abstract: Normal rabbits typically respond to a diet high in cholesterol with a large increase in the concentration of plasma cholesterol. We have previously described the breeding and partial characterization of a variant rabbit which does not respond to a high cholesterol diet with changes in plasma cholesterol concentration. In the present report we have characterized three components involved in cholesterol homeostasis: the B/E (LDL) receptor, 3-hydroxy-3-methylglutaryl coenzyme A reductase activity (HMG-CoA reductase, EC 1.1.1.34) and acyl-coenzyme A: cholesterol acyltransferase activity (ACAT, EC 2.3.1.26) in the livers of the hypercholesterolemia-resistant rabbits. Using normal cholesterol-fed rabbit 125I beta-VLDL as a ligand, liver membranes prepared from resistant rabbits fed a low-cholesterol diet had 70% higher binding capacity than membranes from normal rabbits fed the same diet. Similar experiments demonstrated that the resistant rabbits had a 240% higher B/E receptor binding capacity compared to normal animals when liver membranes were prepared from animals fed a 0.25% cholesterol-enriched diet. No difference in the binding affinity of 125Ibeta-VLDL was detected in membranes prepared from normal or resistant animals. When fed a low-cholesterol diet, the resistant rabbits had approximately 2-fold higher hepatic HMG-CoA reductase activity (97.4 +/- 3.5 pmol product/mg/min in resistant animals compared to 45 +/- 1.1 pmol product/min/mg in normal animals). The difference was exaggerated in animals fed the 0.25% cholesterol-enriched diet, 73.3 +/- 5.5 vs 2.4 +/- 0.56 pmol product/min/mg for resistant and normal membranes respectively. The basal activity of ACAT in hepatic membranes was significantly lower in the resistant rabbits compared to normal rabbits (138 +/- 11 vs 268 +/- 19 pmol cholesteryl ester/min/mg in resistant and normal rabbits respectively); when fed a 0.25% cholesterol-enriched diet, the enzyme was induced 6-fold in normal animals but was increased only 2-fold in the resistant animal. These biochemical data suggested that the resistant rabbit maintained low intracellular cholesterol even when fed a cholesterol-enriched diet. Direct measurement of cellular cholesterol and cholesteryl esters demonstrated that the concentration of these lipids was significantly lower in the resistant animal than in normal animals with the largest differences found in the cytoplasmic rather than the membrane compartment. These studies demonstrate that the resistant rabbit manifests several quantitative differences in cholesterol metabolism and in the regulation of cholesterol metabolism; but these studies do not directly explain the underlying cause of the resistance to hypercholesterolemia in the resistant rabbit. |
| Cholesterol metabolism in liver and gallbladder mucosa of patients with cholesterolosis Sahlin, S., D. Stahlberg, et al. (1995), Hepatology 21(5): 1269-75. Abstract: The objective of this study was to investigate possible pathogenetic factors for cholesterolosis. Liver tissue, gallbladder mucosa, and gallbladder bile were collected in patients with cholesterol gallstones (GS) (14 patients with and 14 patients without cholesterolosis) and gallstone-free (GSF) subjects (11 with and 21 without cholesterolosis) undergoing cholecystectomy. In cholesterolosis, the gallbladder mucosa was characterized by a fivefold increase in esterified cholesterol and normal content of free cholesterol. The hepatic levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, governing cholesterol synthesis, and acyl coenzyme A: acyltransferase activity, catalyzing the esterification of cholesterol, were similar in patients with and without cholesterolosis. Also in the gallbladder mucosa, the 3-hydroxy-3-methylglutaryl coenzyme A reductase activity was similar in patients with and without cholesterolosis. The acyl coenzyme A: acyltransferase activity of the gallbladder mucosa was increased in the GSF subjects with cholesterolosis. The nucleation time of gallbladder bile was shorter in the GSF subjects with cholesterolosis compared with the time of those without cholesterolosis. Occurrence of cholesterol crystals, lipid composition, and cholesterol saturation of gallbladder bile were not significantly influenced by the absence or presence of cholesterolosis. The study has confirmed that cholesterolosis is associated with a several-fold increased level of esterified cholesterol. The data suggest that patients with cholesterolosis have normal hepatic cholesterol formation and esterification. The local synthesis of cholesterol in the gallbladder mucosa seems to be normal. A positive correlation was obtained between the cholesterol saturation of bile and the content of esterified cholesterol in the gallbladder mucosa in the whole series of patients.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Cholesterol metabolism in mature and immature rats fed animal and plant protein De Schrijver, R. (1990), J Nutr 120(12): 1624-32. Abstract: In two feeding experiments immature (180 g) and mature rats (370 g) were fed a semi-purified diet containing 20% of a protein source (casein, wheat gluten, soybean or potato protein) for 4 wk. Food supply was restricted to 15 g daily. As compared to casein, plant proteins induced significantly lower concentrations of plasma total cholesterol and high density lipoprotein (HDL) cholesterol. The plasma cholesterol increase associated with aging was not prevented by consumption of casein, soybean or potato protein, but wheat gluten seemed to be effective. Lecithin-cholesterol acyltransferase (LCAT) activity was not significantly different in rats of the same age fed different plant proteins, whereas the esterification rate was lower in rats fed casein. With aging the LCAT activity generally decreased. As compared to the casein groups, the rats fed plant proteins showed higher excretion of fecal neutral and acidic steroids. Among the groups fed plant proteins, the fecal output of steroids was variable. Significantly negative correlations were found between fecal total sterol excretion and plasma total cholesterol or HDL cholesterol, respectively. Plant proteins showed a faster migration rate in the stomach, whereas their migration and absorption were slower in the first half of the small intestine. A relation between nonabsorbed nitrogen-containing substances and sterol excretion was hypothesized. |
| Cholesterol metabolism in monocyte-derived macrophages from macrophage colony-stimulating factor administered rabbits Ishii, I., T. Kimuro, et al. (1995), Biochim Biophys Acta 1254(1): 51-5. Abstract: The metabolism of beta-very-low-density lipoproteins (beta-VLDL) in macrophages from the blood monocytes of rabbits, which had been administered macrophage colony-stimulating factor (M-CSF) in vivo, was investigated in order to clarify the mechanism of the suppressive effect of M-CSF on cholesterol accumulation in macrophages. Cholesterol ester content after incubation with beta-VLDL, and 3Hcholesterol oleate-beta-VLDL incorporation remarkably increased in cultured macrophages from blood monocytes in the high cholesterol diet control group compared to those in the normal diet control group. Those in macrophages from M-CSF-treated groups, both normal diet and high cholesterol diet, were the same as in the normal diet control group. The ratio of released 3Hcholesterol to incorporated 3Hcholesterol oleate-beta-VLDL in macrophages from control was smaller than that from the M-CSF group. The acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity was enhanced in the high cholesterol diet groups, and the activity in M-CSF-treated groups decreased. The neutral cholesterol esterase activity was enhanced in the M-CSF-treated groups compared with that in the non-treated control groups. These results suggest that high cholesterol diet induced further cholesterol esterification and that M-CSF treatment enhanced cholesterol clearance in macrophages. |
| Cholesterol metabolism in New World primates: comparative studies in two tamarin species (Saguinus oedipus and Saguinus fuscicollis) and the squirrel monkey (Saimiri sciureus) Croll, D. H., L. M. Ausman, et al. (1993), Comp Biochem Physiol B 106(4): 845-53. Abstract: 1. Cholesterol metabolism has been characterized in three species of New World primates, the cotton-top tamarin, the saddle-back tamarin, and the squirrel monkey. 2. When fed a diet containing cholesterol, the three species exhibited differing responses of plasma cholesterol levels. 3. Dietary cholesterol absorption was determined and plasma cholesterol die-away kinetics were analyzed in terms of a two-pool model. 4. The results of the analyses of cholesterol turnover are consistent with the observed species-specific differences in plasma cholesterol values and cholesterol absorption. 5. Cholesterol metabolism differs between the two tamarin species, as well as between the tamarins and the squirrel monkey. 6. Implications of species-specific differences between tamarin species are discussed in terms of the use of tamarin species as animal models for comparative studies of cholesterol metabolism and the etiology of cancer and cardiovascular disease. |
| Cholesterol metabolism in normal and heterozygous familial hypercholesterolemic newborns Vuorio, A. F., T. A. Miettinen, et al. (2002), J Lab Clin Med 140(1): 35-42. Abstract: In heterozygous familial hypercholesterolemia (FH), serum low-density lipoprotein (LDL) cholesterol levels are frequently increased in utero. A unique Finnish FH population, FH-North Karelia (FH-NK), has been identified, providing an excellent opportunity to study the diagnostic significance of cholesterol metabolism in FH. For that purpose, we investigated lipoprotein lipids, cholesterol precursors (squalene, methyl, and demethyl sterols), cholestanol, and plant sterols in FH-NK newborns (n = 5), non-FH siblings (n = 7), and controls (n = 20) at birth and after 1-year follow-up in 8 FH-NK and 5 non-FH children. The sum of concentrations (micrograms per deciliter) of methyl sterol (8-monomethylsterol, methostenol, 8-dimethylsterol, 8,24-dimethylsterol, and lanosterol) and squalene was higher in FH newborns than in non-FH siblings but overlapped with one control case. Cord-blood total or LDL cholesterol values could not be used for diagnostic purposes, whereas 1-year LDL cholesterol values were highly superior to those measured at birth. The methyl sterol ratio in cord blood was 29 to 193 10(2) mmol/mol cholesterol and was undetectable in serum at the age of 1 year; those of the demethyl precursor sterols were 1.5 to 8 times higher in cord blood than in serum at the age of 1 year, suggesting that cholesterol synthesis was markedly increased at birth. Plant sterols, not synthesized in human beings, were already present in serum of all the groups at birth, indicating their transfer, apparently with cholesterol, from mother to fetus. Babies born to FH mothers showed a greater tendency toward accelerated cholesterol synthesis than did those born to FH fathers. Despite signs of markedly high but similar synthesis of cholesterol at birth in FH and non-FH newborns, the diagnosis of FH was questionable by measurement of cholesterol precursors or LDL cholesterol in cord blood. The latter measurement, at the 1-year mark, is superior for diagnostic purposes. |
| Cholesterol metabolism in patients with chronic renal failure on hemodialysis Igel-Korcagova, A., P. Raab, et al. (2003), J Nephrol 16(6): 850-4. Abstract: Premature atherosclerosis is a major concern in patients on chronic dialysis and the identification of risk factors is important for preventive and interventional strategies. Other than the recognized atherogenic lipoprotein levels, little is known about overall cholesterol metabolism in patients on chronic hemodialysis (HD) and the best therapeutic intervention is still being debated. Therefore, we investigated intestinal cholesterol absorption, cholesterol and bile acid synthesis, and non-cholesterol plasma sterols in eight patients on dialysis and compared the results to those of 16 healthy male controls matched for body mass index and dietary cholesterol intake. Total, low-density lipoprotein (LDL) cholesterol, and triglycerides did not differ between the groups, but dialysis patients had a significantly lower high-density lipoprotein (HDL) cholesterol level (39 +/- 11 mg/dL vs. 48 +/- 10 mg/dL, p < 0.045). However, fractional cholesterol absorption, was significantly lower in dialysis patients (42.8 +/- 10.9% vs. 53.4 +/- 11%, p < 0.035), whereas plasma plant sterol concentrations and their ratios to cholesterol did not differ. Bile acid and total cholesterol synthesis were lower in dialysis patients (40% and -25%, respectively), although the differences were not significant. In contrast, lathosterol and its ratio to cholesterol in plasma was significantly lower in dialysis patients (0.176 +/- 0.084 mg/dL vs. 0.251 +/- 0.102 mg/dL, p < 0.024 and 0.733 +/- 0.353 microg/mg vs. 1.172 +/- 0.407 microg/mg, p < 0.017, respectively), indicating reduced hepatic de novo cholesterol synthesis. It is concluded that reduced HDL cholesterol and reduced bile acid synthesis contributes to atherosclerosis pathogenesis in dialysis patients, whereas intestinal cholesterol absorption and hepatic cholesterol synthesis did not seem dominant in this process at this stage of disease. Consequently, treatment with bile acid binding resins could be preferable to treatment with cholesterol absorption and synthesis inhibitors. |
| Cholesterol metabolism in patients with ischemic heart disease with varying supplies of omega-3 polyunsaturated fatty acids Samsonov, M. A., B. G. Liapkov, et al. (1994), Vopr Med Khim 40(5): 55-9. Abstract: Patients with ischemic heart disease and with hyperlipidemia of the IIa, IIb and IV types as well as not exhibiting any pronounced alterations in cholesterol metabolism were treated with various amounts of omega-3 polyunsaturated fatty acids (PUFA) introduced into the basic antiatherosclerotic diet: 1 group--content of the essential factor 0.2 g/day, 2 group--increased content of natural products with PUFA up to 1 g/day, 3 group--increased PUFA content due to the drug "euconol" 5 g/day. Administration of the PUFA omega-3 into the basic antiatherosclerotic diet contributed to development of adequate clinico-biochemical alterations; under these conditions content of alpha-cholesterol in blood correlated directly to concentration of polyunsaturated cholesterol esters and PUFA omega-3 (eicosapentaenate and docosahexaenate) as well as reverse correlation was found between content of total cholesterol and these molecular forms of cholesterol esters studied. Enrichment of the diet with PUFA omega-3 did not cause any alterations in content of primary bile acids in blood thus suggesting that PUFA omega-3 did not affect the cholesterol catabolism. These data enabled us to plot the graph for individual evaluation of cholesterol metabolism in patients with ischemic heart disease involving alterations in the spectrum of esterified cholesterols in blood before and after the treatment course. |
| Cholesterol metabolism in primary biliary cirrhosis during simvastatin and UDCA administration Del Puppo, M., M. Galli Kienle, et al. (2001), J Lipid Res 42(3): 437-41. Abstract: Little is known about the effects of cholesterol-lowering agents in hypercholesterolemic patients with primary biliary cirrhosis (PBC). The aim of this study was to compare the changes induced by simvastatin and ursodeoxycholic acid (UDCA) on cholesterol metabolism in patients with PBC and preserved liver function. Six patients with PBC were administered simvastatin (40 mg/day) for 30 days and, after a washout period of 30 days, ursodeoxycholic acid (600 mg/day) for 30 days. Serum levels of lathosterol, campesterol, 7 alpha-hydroxycholesterol, and 27-hydroxycholesterol were measured by gas chromatography-mass spectrometry. During simvastatin administration, reduction of cholesterol levels (34% in 30 days) was paralleled by the decrease of lathosterol (55%), whereas concentrations of campesterol and of the two hydroxysterols were not substantially modified. During ursodeoxycholic acid administration, a trend toward a decrease of serum cholesterol concentrations was observed after only one year of treatment, and these changes were paralleled by the decrease of campesterol serum levels. Both simvastatin and UDCA were well tolerated, and a reduction of serum liver enzyme levels occurred with the latter.Simvastatin proved to be safe and effective in reducing serum cholesterol levels in patients with PBC by an inhibitory effect on cholesterol synthesis occurring within 24 h. --Del Puppo, M., M. Galli Kienle, A. Crosignani, M. L. Petroni, B. Amati, M. Zuin, and M. Podda. Cholesterol metabolism in primary biliary cirrhosis during simvastatin and UDCA administration. J. Lipid Res. 2001. 42: 437--441. |
| Cholesterol metabolism in rat adrenal gland during reversible endotoxic shock Abarca, S. and R. Garcia (1993), Eur J Biochem 211(3): 829-34. Abstract: The adrenal glands have a crucial role for survival during endotoxic shock. Cholesterol is the obligatory intermediary in corticosteroid biosynthesis; thus any alteration in either the availability of cholesterol or in the ability of the adrenal gland to use cholesterol would have a profound effect on corticosteroid production. We have studied the effect of Escherichia coli endotoxin on cholesterol metabolism, injecting lipopolysaccharide (1.6 mg/100 g body) from E. coli 0111:B4 into the tail vein of male Wistar rat. Previous studies from this laboratory have shown that this dose of lipopolysaccharide induces a reversible endotoxic shock. During reversible endotoxic shock there is an alteration in plasma cholesterol; plasma total-cholesterol levels increase mainly at 6-24 h post-lipopolysaccharide injection, whereas cholesterol in high-density lipoproteins shows no significant variations, except a slight but significant decrease at 24 h. The cholesterol content in adrenal gland is diminished in endotoxemic rat, this decrease is more important at 6-24 h after endotoxin injection. We have also measured the acyl-CoA:cholesterol O-acyltransferase (ACAT) and cholesterol-esterase (CEH) activity during endotoxic shock. ACAT activity decreases after lipopolysaccharide injection. ACAT activity in endotoxemic rats is approximately 35-40% of the activity in control rats. This decrease is due to a defect in the functional capacity of the enzyme, since with exogenous cholesterol there is no significant variation in the ACAT activity. CEH activity, in contrast, increases during endotoxic shock; it shows a maximum (twofold the activity seen in control rats) at 6 h after lipopolysaccharide injection. These results show that lipopolysaccharide injection modifies cholesterol metabolism in plasma and in the adrenal gland, either directly or by mediators. |
| Cholesterol metabolism in rat is affected by protocatechuic acid Tamura, A., M. Fukushima, et al. (2004), J Nutr Sci Vitaminol (Tokyo) 50(1): 13-8. Abstract: The effects of protocatechuic acid on serum cholesterol and gene expression related to cholesterol metabolism in rats were investigated. Rats were fed a cholesterol-free diet with or without 5 g protocatechuic acid/kg diet for 4 wk. There were no significant differences in body weight and food intake among groups through the experimental period. The liver weight in the protocatechuic acid group was significantly lower than that in the control group. The serum total cholesterol, high-density lipoprotein (HDL)-cholesterol and very low-density lipoprotein (VLDL)+intermediate density lipoprotein (IDL)+low-density lipoprotein (LDL)-cholesterol concentrations in the protocatechuic acid group were significantly lower than those in the control group through the feeding period. The hepatic cholesterol concentration in the protocatechuic acid group was significantly higher than in the control group at the end of the 4-wk feeding period. The relative hepatic LDL receptor, apo B, apo E, lecithin-cholesterol acyltransferase (LCAT) and hepatic triglyceride lipase (HTGL) mRNA levels in the protocatechuic acid group were significantly higher than those in the control group. The results of this study suggest the possibility that the increase in the hepatic LDL receptor, apo E, LCAT and HTGL guessed by these mRNAs increase in the protocatechuic acid group lowers the serum total cholesterol level. |
| Cholesterol metabolism in the brain Dietschy, J. M. and S. D. Turley (2001), Curr Opin Lipidol 12(2): 105-12. Abstract: The central nervous system accounts for only 2% of the whole body mass but contains almost a quarter of the unesterified cholesterol present in the whole individual. This sterol is largely present in two pools comprised of the cholesterol in the plasma membranes of glial cells and neurons and the cholesterol present in the specialized membranes of myelin. From 0.02% (human) to 0.4% (mouse) of the cholesterol in these pools turns over each day so that the absolute flux of sterol across the brain is only approximately 0.9% as rapid as the turnover of cholesterol in the whole body of these respective species. The input of cholesterol into the central nervous system comes almost entirely from in situ synthesis, and there is currently little evidence for the net transfer of sterol from the plasma into the brain of the fetus, newborn or adult. In the steady state in the adult, an equivalent amount of cholesterol must move out of the brain and this output is partly accounted for by the formation and excretion of 24S-hydroxycholesterol. This cholesterol turnover across the brain is increased in neurodegenerative disorders such as Alzheimer's disease and Niemann-Pick type C disease. Indirect evidence suggests that large amounts of cholesterol also turn over among the glial cells and neurons within the central nervous system during brain growth and neuron repair and remodelling. This internal recycling of sterol may involve ligands such as apolipoproteins E and AI, and one or more membrane transport proteins such as members of the low density lipoprotein receptor family. Changes in cholesterol balance across the whole body may, in some way, cause alterations in sterol recycling and apolipoprotein E expression within the central nervous system, which, in turn, may affect neuron and myelin integrity. Further elucidation of the processes controlling these events is very important to understand a variety of neurodegenerative disorders. |
| Cholesterol metabolism in the livers of chick embryos produced from immature birds Vajda, K., J. H. Shand, et al. (1994), Biochem Soc Trans 22(4): 431S. |