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PubMed1972

Cholesterol metabolism in the macrophage. 3. Ingestion and intracellular fate of cholesterol and cholesterol esters.

Phagocytosis of cholesterol-containing particles resulted in the formation of an intralysosomal cholesterol compartment. Cholesterol was excreted out of the macrophage with a single exponential rate which depended on the concentration of acceptor lipoproteins in the medium. Exchange kinetics performed on cells which had ingested particulate cholesterol suggested that excretion occurred by the same mechanism as exchange. Cholesterol esters as particulate albumin coacervates were taken up by macrophages and hydrolyzed by a lysosomal cholesterol esterase with optimal activity at pH 4.0. Cholesteryl linoleate was hydrolyzed much more readily than cholesteryl palmitate. The amount of cholesterol esterase and its specific activity increased during the in vitro cultivation of macrophages. Intralysosomally, cholesteryl linoleate and palmitate were hydrolyzed to free cholesterol which was excreted from the macrophage and recovered in the medium. Since cholesteryl linoleate was hydrolyzed more rapidly than free cholesterol was excreted into the medium, free cholesterol accumulated intralysosomally. Cholesteryl palmitate was hydrolyzed more slowly, and the rate of hydrolysis was limiting for excretion of the free cholesterol from within the lysosome.

Acid Phosphatase↗
PubMed2003

Increase in cholesterol and cholesterol oxidation products, and role of cholesterol oxidation products in kainate-induced neuronal injury.

Little is known about changes in sterols, in particular cholesterol, and cholesterol oxidation products (COPs) in oxidative injury in neural tissues. We have therefore examined changes in cholesterol and COPs using a model of excitotoxic injury. Intracerebroventricular injections of kainate in rats resulted in an increase in immunoreactivity to cholesterol in the affected CA fields of the hippocampus. The increase was confirmed by increased filipin staining of cholesterol in adjacent sections from the same animals, and in hippocampal slice or neuronal cultures after kainate treatment. In neuronal cultures, addition of lovastatin, an inhibitor of cholesterol synthesis, attenuated the increased filipin staining after kainate treatment, indicating that the increase in cholesterol could involve increased cholesterol synthesis. Furthermore, gas chromatographic mass spectrometric (GC/MS) analysis of cholesterol and COPs in kainate-injected rat brain showed a marked increase in cholesterol and COPs including 7-ketocholesterol, 3 days after kainate treatment. The addition of some COPs, including 7-ketocholesterol and cholesterol epoxides to hippocampal slices resulted in neuronal injury as reflected by decreased staining of a neuronal marker in the affected CA fields. The ability of these COPs to produce neuronal injury was attenuated by glutathione, suggesting that oxidative mechanisms are involved in neuronal injury induced by these products. These results, together with GC/MS results that showed significant increase in 7-ketocholesterol at 3 days post-kainate injury suggest that 7-ketocholesterol may be a factor in aggravating oxidative damage to neurons, after the initial stages of kainate-induced neuronal injury.

Animals↗
PubMed1984

Regulation of cholesterol metabolism in rat adrenal glands: effect of adrenocorticotropin, cholesterol, and corticosteroids on acyl-coenzyme A synthetase and cholesterol ester hydrolases.

The regulation of cholesterol metabolism in rat adrenal glands, especially the effect of ACTH, cholesterol, and corticosteroids on acyl-coenzyme A (CoA) synthetase and cholesterol ester hydrolases was investigated. A significant increase in acyl-CoA synthetase activity and decrease in cholesterol ester hydrolase activities were observed in 24-h hypophysectomized rats. Acute injection of ACTH, however, reversed these changes, whereas dexamethasone administration had no effect. When 4-aminopyrazolo[3,4-d]pyrimidine was given to rats, adrenal cholesterol ester content and the acyl-CoA synthetase activity declined and the activities of the cholesterol ester hydrolases were increased in association with the rise of plasma ACTH concentration. When dexamethasone, which suppresses ACTH secretion, was simultaneously administered with 4-aminopyrazolo[3,4-d]pyrimidine no changes except for a decrease in plasma cholesterol level occurred. In hyperlipidemic rats the acyl-CoA synthetase activity increased when a high cholesterol diet was given and the plasma cholesterol level was increased. These results suggest that acyl-CoA synthetase is under the influence of ACTH and also the plasma cholesterol concentration, and that cholesterol ester hydrolases are mainly regulated by ACTH.

Adenine↗
PubMed1995

Hypocholesterolemic action and prevention of cholesterol absorption via the gut by F-1394, a potent acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, in cholesterol diet-fed rats.

In the present study, we investigated the hypocholesterolemic effect of F-1394 ((1s,2s)-2-[3-(2,2-dimethylpropyl)-3-nonylureido]aminocycloh exane-1-yl 3-[N-(2,2,5,5-tetramethyl-1,3-dioxane-4-carbonyl)amino] propionate), a potent and selective inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT), and the effect on cholesterol absorption via the gut in rats fed a 1% cholesterol diet. Single administration of F-1394 to the cholesterol diet-fed rats at the doses of 3-30 mg/kg, p.o. decreased the serum cholesterol levels by 16-54% 3 hr after the administration. The ACAT activity in the small intestinal mucosa of the rats given orally F-1394 (30 mg/kg) was significantly inhibited 3 hr after the administration. The hypocholesterolemic action of F-1394 had a faster onset than that of DL-melinamide or CL-277,083. The study by the dual isotope ratio method showed that F-1394 (30 mg/kg, p.o.) significantly suppressed the dietary cholesterol absorption. Furthermore, in the determination of cholesterol absorption by using 14C-cholesterol as the oral tracer, the administration of F-1394 (30 mg/kg, p.o.) 1 or 2 hr before or immediately after the application of the oral tracer significantly prevented the appearance of the radioactivity in the circulation by around 90%. These results indicate that oral administration of F-1394 inhibits the ACAT activity in the small intestinal mucosa and subsequently contributes much to the prevention of cholesterol absorption via the gut, resulting in the decrease in serum cholesterol levels in the cholesterol diet-fed rats. Furthermore, the effect of F-1394 appears immediately after its administration in contrast to that of DL-melinamide or CL-277,082.

Administration, Oral↗
PubMed1987

Cholesterol sulfate inhibits adrenal mitochondrial cholesterol side chain cleavage at a site distinct from cytochrome P-450scc. Evidence for an intramitochondrial cholesterol translocator.

Cholesterol sulfate inhibits (K1/2, 6 microM) the side chain cleavage of exogenous cholesterol in intact rat adrenal mitochondria. Inhibition is at a site other than cytochrome P-450scc: the spin state of the hemoprotein is not perturbed, and its activity is unaffected as judged by the failure to inhibit the metabolism both of 25-hydroxycholesterol and of endogenous cholesterol in a mitochondrial "steroidogenic pool." In contrast, 25-hydroxycholesterol, known to interact with the cytochrome, prevented the cleavage of both endogenous and exogenous cholesterol and produced the expected optical changes in the hemoprotein. Inhibition was specific, since a variety of related compounds including pregnenolone sulfate were not effective. Metabolic conversion to other species was insufficient to account for inhibition, indicating that cholesterol sulfate is the effective molecule. A hallmark of an inhibitor of a transport system is that disruption of the barrier to transport eliminates inhibition. Sonic disruption of mitochondria abated by 70% the effect of cholesterol sulfate, but did not affect inhibition by 25-hydroxycholesterol. Thus, the cholesterol sulfate appears to inhibit an intramitochondrial cholesterol translocation system that functions to move cholesterol into a steroidogenic pool. The high content of cholesterol sulfate in adrenal cortex (Drayer, N.M., Roberts, K.D., Bandi, L., and Lieberman, S. (1964) J. Biol. Chem. 239, 3112-3114) suggests a possible regulatory role for this molecule.

Adrenal Glands↗
PubMed1997

Apoprotein E phenotype determines serum cholesterol in infants during both high-cholesterol breast feeding and low-cholesterol formula feeding.

Our objective was to establish the role of the apoprotein (apo) E phenotype in determining serum cholesterol levels in infants fed exclusively on high-fat, high-cholesterol human milk and in those fed a low-cholesterol, high-unsaturated fat formula. The total and lipoprotein cholesterol, apoB, and triglyceride concentrations in serum were quantified and related to the apoE phenotype in 151 infants at birth and at 2, 6, 9, and 12 months of age. Forty-four had the E3/4 or 4/4 phenotype (E4 group), 94 had the E3/3 phenotype (E3 group), and 13 had the E2/3 or 2/4 phenotype (E2 group). In cord blood, cholesterol concentrations tended to be higher in the E4 than in the E2 group. With exclusive breast-feeding, the concentrations rose significantly faster and higher in the E4 group than in the E3 group or, especially, the E2 group. The values (mmol/L, mean +/- SEM) were 1.6 +/- 0.15, 1.5 +/- 0.05, 1.4 +/- 0.1 (P = n.s.) at birth; 4.2 +/- 0.1, 3.8 +/- 0.08, 3.4 +/- 0.2 (P < 0.001) at 2 months; 4.4 +/- 0.15, 3.9 +/- 0.1, 3.4 +/- 0.15 (P < 0.001) at 4 months; 4.3 +/- 0.17, 4.0 +/- 0.13, 3.7 +/- 0.26 (P < 0.001) at 6 months; 4.8 +/- 0.28, 4.4 +/- 0.11, 3.8 +/- 0.05 (P < 0.001) at 9 months; and 4.7 +/- 0.11, 4.4 +/- 0.08, 4.1 +/- 0.19 (P < 0.001) at 12 months, for the E4, E3, and E2 groups, respectively. Increases in LDL cholesterol and LDL apoB behaved similarly. The total triglyceride, and total HDL, HDL2, and HDL3 cholesterol concentrations did not depend on the apoE phenotype. Among infants fed high-fat, high-cholesterol human milk, the total and LDL-cholesterol concentrations and the LDL apoB concentration of those with the apoE phenotype 4/4 or 3/4 rose faster and to higher levels than in other infants. Among formula-fed infants, receiving a low-cholesterol, high-unsaturated fat diet, the differences between the apoE groups were smaller.

Aging↗
PubMedDate not supplied

Corn husk oil lowers plasma LDL cholesterol concentrations by decreasing cholesterol absorption and altering hepatic cholesterol metabolism in guinea pigs.

To test the hypocholesterolemic mechanisms of corn husk oil (CoHO), male Hartley guinea pigs were fed diets containing increasing doses of CoHO, either 0 (control), 5, 10, or 15 g/100 g, and 0.25 g/100 g cholesterol. A positive control group (LC) with low dietary cholesterol (0.04 g/100 g) was also included. Fat was adjusted to 15 g/100 g in all diets by the addition of regular corn oil. Plasma low density lipoprotein (LDL) cholesterol concentrations were 32, 55, and 57% (P < 0.0005) lower with increasing doses of CoHO. In addition, intake of CoHO resulted in 32 to 43% lower hepatic total and esterified cholesterol and 55 to 60% lower triacylglycerol concentrations compared with the control group (P < 0.01). CoHO intake resulted in plasma and hepatic cholesterol concentrations similar to those in guinea pigs from the LC group. The number of cholesteryl ester and free cholesterol molecules was higher in LDL from the control group than in LDL from the CoHO or the LC groups. Hepatic beta-hydroxy-beta-methylglutaryl-coenzyme A reductase activity was not modified by CoHO intake whereas cholesterol 7alpha-hydroxylase was up-regulated by 45 to 49% (P < 0.01) in the 10 and 15 g/100 g CoHO groups. Hepatic acyl coenzyme A cholesterol acyltransferase activity was down-regulated in a dose-dependent manner by 54, 58, and 63% with increasing doses of CoHO. CoHO intake resulted in increased fecal cholesterol excretion by 40 to 55% compared with the control and LC groups. Total fecal neutral sterol excretion was enhanced 42 to 55% by CoHO compared with the control group and by 59 to 68% compared with the LC group. The data from these studies suggest that CoHO has its hypocholesterolemic effect by decreasing cholesterol absorption and increasing bile acid output. These alterations in the intestinal lumen alter hepatic cholesterol metabolism and may affect the synthesis and catabolism of lipoproteins.

Journal Article↗
PubMed1981

[Effect of high-fat diet on the contents of total cholesterol, free cholesterol and esterified cholesterol in the serum and liver of rats].

Four-week-old male Wister Rats were fed a diet containing 50% of fat up to the age of 9 weeks and 6 months, respectively. The control group received a diet with 3% of fat. The fat consisted of lard (1/3) and sunflower oil (2/3). Serum cholesterol was determined according to the standard method 1 of the DAB 7 (German Pharmacopoeia); liver cholesterol was estimated by the method of Naito and Lewis. As compared to the control animals, the 9-week-old rats on the high-fat diet showed serum cholesterol values (total, free and esterified cholesterol) which were significantly lower. There was no difference in serum cholesterol level between the 6-month-old rats on the high-fat diet and the control animals. In contrast to this, the liver cholesterol levels of the 9-week-old and the 6-month-old rats on the high-fat diet were significantly increased. In both age-groups the ratio of free cholesterol to esterified cholesterol was changed in favour of the esterified cholesterol. The present results confirm the findings reported in the literature, except for the unchanged serum cholesterol values observed by the authors in the long-time dietary experiment.

Animals↗
PubMed1991

Cholesterol feeding increases plasma and aortic tissue cholesterol oxide levels in parallel: further evidence for the role of cholesterol oxidation in atherosclerosis.

To determine the relationship between plasma and arterial wall oxysterols, plasma and aortic tissue from 7 New Zealand White rabbits fed a high cholesterol (1%) diet for 6 weeks was compared to plasma and aortic tissue from 7 normocholesterolemic rabbits fed standard rabbit chow. Cholesterol and cholesterol oxide fractions were isolated and analyzed by gas chromatography. Normocholesterolemic plasma and aortic tissue contained low levels of cholest-5-ene-3 beta, 7 alpha-diol, cholesta-3,5-dien-7-one, 5,6 alpha-epoxy-5 alpha-cholestan-3 alpha-ol, cholest-5-ene-3 beta, 7 beta-diol, and 5 alpha-cholestane-3 beta, 5,6 beta-triol while hypercholesterolemic plasma and atherosclerotic aorta contained significantly higher levels (P less than 0.05) of these products. Furthermore, 5,6 beta-epoxy-5 alpha-cholestan-3 beta-ol not found in normocholesterolemic plasma or aortic tissue was present in substantial amounts in both hypercholesterolemic plasma and atherosclerotic aortic tissue. Cholest-5-ene-3 beta,25-diol and 3 beta-hydroxycholest-5-ene-7- one not present in normocholesterolemic aorta were present in the atherosclerotic aorta. The oxysterol chromatographic patterns of normocholesterolemic plasma and normocholesterolemic aortic tissue were similar to each other as were the oxysterol chromatographic patterns of hypercholesterolemic plasma and atherosclerotic aortic tissue. The chromatographic patterns between the normocholesterolemic and hypercholesterolemic samples differed however. Possible absorption of the low levels of cholesterol oxides present in the cholesterol feed could account for the elevation of only some of the oxysterols. We conclude that cholesterol oxides exist at some basal level in normocholesterolemia and that these levels are increased by cholesterol-feeding which results in hypercholesterolemia. Our findings demonstrate that there is a strong relationship between plasma and aortic arterial wall levels of cholesterol oxides and suggest that in addition to exogenous sources, formation of cholesterol oxides proceeds via free radical oxidation acting upon elevated cholesterol levels resulting in the accumulation of these potentially cytotoxic and atherogenic products.

Animals↗
PubMed2006

A green tea extract lowers plasma cholesterol by inhibiting cholesterol synthesis and upregulating the LDL receptor in the cholesterol-fed rabbit.

Green tea extracts enriched in catechins decrease plasma cholesterol in hamsters, mice and rats. The aims of this study were to determine whether a catechin-enriched extract of green tea could lower plasma cholesterol in the cholesterol-fed rabbit and to determine the mechanism of action. Four groups of six New Zealand White rabbits were initially made hypercholesterolaemic by feeding a 0.25% (w/w) cholesterol diet for 2 weeks before the diet was supplemented with a catechin extract from green tea at 0, 0.5, 1 or 2% (w/w) for 4 weeks. Administration of the crude catechin extract from green tea significantly (p<0.05) lowered cholesterol in plasma (-60%), VLDL+IDL (-70%), LDL (-80%), liver (total by -25% and unesterified by -15%) and aorta (-25%) compared to control. There was a significant reduction in the cholesterol synthesis index (-60%) and a significant increase in hepatic LDL receptor activity (+80%) and protein (+70%) but there was no change in the intrinsic capacity to absorb cholesterol from the intestines. These results suggest that green tea catechins lowered plasma, liver and aortic cholesterol in the cholesterol-fed rabbit by lowering cholesterol synthesis and upregulating the hepatic LDL receptor.

Animals↗
PubMed1991

Pioglitazone hydrochloride inhibits cholesterol absorption and lowers plasma cholesterol concentrations in cholesterol-fed rats.

Diabetes is associated with altered cholesterol metabolism that may contribute to cardiovascular complications. Treatment of rats with pioglitazone hydrochloride, a novel antidiabetic compound that improves the general response of target cells to insulin, significantly lowered cholesterol levels in rats fed a hypercholesterolemic diet and produced a significant reduction in cholesterol absorption. Drug treatment was ineffective in rats that were not given dietary cholesterol. To determine whether these effects of pioglitazone hydrochloride might be related to the known ability of this compound to improve the response to circulating insulin, similar studies were conducted in streptozocin-induced diabetic rats with and without insulin replacement. Diabetic rats absorbed a greater percentage of dietary cholesterol than control rats. Treatment of insulin-deficient diabetic rats with pioglitazone alone did not affect cholesterol absorption; however, the combination of insulin and pioglitazone was synergistic to lower absorption of cholesterol and circulating cholesterol and triglycerides. Treatment of either normal rats or diabetic rats receiving insulin with pioglitazone hydrochloride produced a twofold decrease in the ratio of total cholesterol to high-density lipoprotein cholesterol. These results suggest that treatments that improve insulin sensitivity may also have a positive impact on coronary artery disease associated with diabetes.

Animals↗
PubMed1990

Day-to-day variability of serum cholesterol, triglyceride, and high-density lipoprotein cholesterol levels. Impact on the assessment of risk according to the National Cholesterol Education Program guidelines.

The National Cholesterol Education Program has recently published guidelines for the assessment of cardiovascular risk and goals for laboratory accuracy. To test the impact of biologic and analytic variability on the ability of a single lipid measurement to assess risk accurately, lipids were measured on three occasions in 51 volunteers. Notable day-to-day variability of total cholesterol (5%), triglyceride (20%), high-density lipoprotein cholesterol (10%), and calculated low-density lipoprotein cholesterol (8%) levels was found. Analytic variability contributed significantly to total variability of high-density lipoprotein cholesterol levels and calculated low-density lipoprotein cholesterol levels. Confidence intervals constructed around National Cholesterol Education Program cutoff points suggested that classification was reliable from a single measurement if total cholesterol value was below 4.78 (less than 185 mg/dL), between 5.56 and 5.81 (215 and 225 mg/dL), or above 6.59 mmol/L (greater than 225 mg/dL). Low-density lipoprotein cholesterol value classification from a single measurement was only accurate at below 3.00 (greater than 116 mg/dL) or above 4.50 mmol/L (greater than 174 mg/dL). This study documents significant day-to-day variability of serum lipids and suggests that patients near the National Cholesterol Education Program cutoff points may require repeated measurements to assign risk accurately.

Adult↗
PubMed1985

Familial aortic aneurysms: serum concentrations of triglyceride, cholesterol, HDL-cholesterol and (VLDL + LDL)-cholesterol.

Patients with abdominal aortic aneurysms (AAAs) have been compared with healthy controls with respect to the serum concentrations of triglyceride, cholesterol, HDL-cholesterol and (VLDL + LDL)-cholesterol. The concentrations of triglyceride and (VLDL + LDL)-cholesterol in serum were higher in the patients than in the controls, while the concentration of HDL-cholesterol in serum was lower in the patients than in the controls. There was no statistically significant difference in the serum concentration of total cholesterol between the patients and the controls. Twelve patients had first degree relatives (brothers, sisters and/or parents) with AAAs and six patients had second degree relatives (cousins or brothers and sisters of the parents) with AAAs. There was no statistically significant difference between the patients who had first degree relatives with AAAs and the patients without AAAs in the family in the serum concentrations of triglyceride, cholesterol, HDL-cholesterol and (VLDL + LDL)-cholesterol.

Aged↗
PubMed1983

Lecithin:cholesterol acyltransferase-mediated modification of discoidal peripheral lymph high density lipoproteins: possible mechanism of formation of cholesterol-induced high density lipoproteins (HDLc) in cholesterol-fed dogs.

Peripheral lymph high density lipoproteins (HDL) of the cholesterol-fed dog differ in a number of characteristics from plasma HDL of the same animal. Their high content of free cholesterol, phospholipid, apoprotein E, and apoprotein A-IV, their greater heterogeneity in size, and the presence of many discoidal particles suggest that a portion of lymph HDL is assembled within the interstitial fluid. The present experiments demonstrate that the endogenous lecithin:cholesterol acyltransferase (LCAT) activity of whole peripheral lymph of the cholesterol-fed dog is far less (less than 1%) than that found in the plasma of the same animal (0.3 nmol/hr per ml versus 40.6 nmol/hr per ml). Addition of partially purified LCAT to whole lymph induced many changes in the chemical composition of peripheral lymph lipoproteins. After incubation with LCAT, the free cholesterol and phospholipid contents of lymph HDL decreased, from 17% to 12% and from 46% to 33%, respectively, whereas cholesteryl ester content increased from 7% to 13%. These changes were accompanied by a mass transfer of apoprotein E and cholesterol to the p less than 1.05 g/ml fraction, the complete disappearance of the discoidal particles, and a decrease in size heterogeneity of lymph HDL. These results suggest that, in the cholesterol-fed dog, cholesterol efflux into the interstitial spaces may occur in the absence of significant LCAT activity. Furthermore, our studies suggest that the subsequent reaction between lymph HDL and LCAT within the vascular compartment leads to the generation of apoprotein E and cholesteryl ester-rich cholesterol-induced HDL.

Animals↗
PubMed1992

Pravastatin lowers serum cholesterol, cholesterol-precursor sterols, fecal steroids, and cholesterol absorption in man.

Serum lipids, and absorption, intestinal fluxes, fecal elimination, and synthesis of cholesterol were studied before and during 4 weeks of pravastatin treatment at a dose of 40 mg/d in heterozygous familial hypercholesterolemic (FH) patients without (control group, n = 7) and with an ileal bypass (IBP group, n = 6). The drug reduced serum total and low-density lipoprotein (LDL) cholesterol and LDL-apoprotein (apo)B levels up to 34%. Less-consistent decreases in intermediate-density lipoprotein (IDL) and very-low-density lipoprotein (VLDL) cholesterol were also seen. None of the control patients and two of the IBP patients became normolipidemic (LDL less than 4 mmol/L). Marked transient reductions in serum free-methylated-cholesterol precursors, and more-constant decreases in the esterified and total fractions, suggested that cholesterol synthesis was reduced shortly after the start of treatment. The decreases in total lathosterol and methylsterols were more extensive in the IBP group than in the control group. Serum plant sterol levels were slightly increased, with inconsistent elevations of cholestanol. Reduced fecal elimination of cholesterol and its precursors suggests that decreased cholesterol synthesis was mainly due to lowered bile acid production, particularly in the IBP group with markedly enhanced basal bile acid and cholesterol synthesis. The serum and fecal levels of cholesterol precursors, lathosterol in particular, were related to each other and were proportionate to the serum level and fecal elimination of cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Effect of phospholipids and bile acids on cholesterol nucleation time and vesicular/micellar cholesterol in gallbladder bile of patients with cholesterol stones.

Supersaturation and rapid nucleation of cholesterol in bile are of key importance in the pathogenesis of cholesterol gallstones. While the effects of bile acids and phospholipids on cholesterol saturation of bile have been extensively studied, their influence on the cholesterol nucleation time has not been compared. We, therefore, investigated whether increases of bile acid or phospholipid concentrations in bile by in vitro supplementation affect the cholesterol nucleation time. Bile samples were obtained at surgery from patients with cholesterol gallstones. Prior to the nucleation assay the bile samples were divided into 0.5-ml aliquots and supplemented with 1.25, 2.5, 5.0, and 10.0 mumol/ml of different phosphatidylcholines (PC-dimyristoyl, PC-dipalmitoyl, PC-distearoyl, and extracted biliary PCs) or with 5.0, 10.0, and 20.0 mumol/ml of bile acids (glycine or taurine conjugates of cholic acid, deoxycholic acid, or chenodeoxycholic acid). The increase of phosphatidylcholine or bile acid concentration decreased the mean cholesterol saturation index to a similar extent (PC: 0.1-0.3; BA: 0.1-0.2). Supplementations of bile with increasing amounts of synthetic or biliary PCs caused a marked prolongation of the nucleation time in bile from 1.5 +/- 0.2 up to > or = 21 days or 2.5 +/- 0.7 up to > or = 21 days. Concurrently, biliary cholesterol was shifted from vesicles to mixed micelles and the cholesterol/phospholipid ratio of the remaining vesicles was progressively lowered. In contrast, the addition of bile acids to gallbladder bile did not affect the cholesterol nucleation time (2.2 +/- 0.3 days), the percentage of vesicular cholesterol, or the cholesterol/phospholipid ratio of vesicles and micelles.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile Acids and Salts↗
PubMed1989

Cholesterol sulfate: a naturally-occurring inhibitor of cholesterol side-chain cleavage which functions at the level of intramitochondrial cholesterol translocation.

Cholesterol sulfate is a naturally occurring compound which is widely distributed among various tissues including the adrenal cortex. When added to adrenal mitochondria from ether-stressed rats, it inhibits pregnenolone synthesis from exogenous but not endogenous cholesterol. Evidence supports a locus of action at the level of an intramitochondrial cholesterol translocation system with no effect on the side-chain cleavage enzymatic system (cytochrome P-450scc). Levels of endogenous cholesterol sulfate in the adrenal are similar to the Ki for inhibition by this compound, suggesting a possible physiological role. Moreover, quantities of cholesterol sulfate present in isolated mitochondria from ether-stressed animals are variable, and levels correlate inversely with rates of pregnenolone production by these preparations. In the presence of malate, mitochondrial cholesterol sulfate is metabolized slowly to pregnenolone sulfate, and its removal correlates with activation of cholesterol side-chain cleavage. Cholesterol sulfate levels are not regulated acutely by stress, but can be decreased significantly after several weeks of daily injection of ACTH (a model of chronic stress). Such treatments result in an increased capacity of isolated adrenal mitochondria to synthesize pregnenolone, and increased activity correlates with increased levels of circulating corticosterone. Thus, we propose that cholesterol sulfate is a new physiological regulator of steroid hormone biosynthesis which may function to regulate the magnitude of the steroidogenic response of the adrenal cortex to ACTH.

Adrenal Cortex↗
PubMed2006

Naringin time-dependently lowers hepatic cholesterol biosynthesis and plasma cholesterol in rats fed high-fat and high-cholesterol diet.

The flavonoid naringin was investigated for its differential effects on hepatic cholesterol regulation when supplemented for 3 weeks and 6 weeks. Sprague-Dawley rats were fed a high-fat and high-cholesterol diet with or without 0.02% naringin supplement for 3 or 6 weeks. Supplementation with naringin resulted in a significant decrease in the plasma cholesterol and triglyceride concentrations in the 6-week trial. Although high-density lipoprotein (HDL)-cholesterol was not altered in either trial, the HDL-cholesterol/total cholesterol ratio (in percent) was significantly higher, and the atherogenic index was significantly lower in the naringin-supplemented groups in the 6-week trial. The hepatic cholesterol content was also lowered by naringin supplementation only in the 6-week trial. The hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity was lower in the rats supplemented with naringin for 6 weeks, while the hepatic acyl-coenzyme A:cholesterol acyltransferase activity was lower in both the 3-week and 6-week trials. Results indicate that supplementation with naringin for 3 weeks did not exhibit a hypolipidemic effect when given with a HFHC diet. Naringin can, however, be beneficial for lowering hepatic cholesterol biosynthesis and levels of plasma lipids when supplemented for 6 weeks in this animal model.

Animals↗