PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Cholesterol”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1979

Regulation of biliary cholesterol output in the rat: dissociation from the rate of hepatic cholesterol synthesis, the size of the hepatic cholesteryl ester pool, and the hepatic uptake of chylomicron cholesterol.

These studies were designed to determine the importance of the rate of hepatic cholesterol synthesis, the size of the hepatic cholesteryl ester pool, the amount of chylomicron cholesterol reaching the liver, and the rate of bile acid transport into bile as determinants of the rate of biliary cholesterol output. Female rats that had been subjected to diurnal light cycling, fasting for 48 hr, intravenous administration of chylomicrons, and diets containing either cholestyramine, cholesterol, or bile acid underwent total biliary diversion for 2 hr. The animals were then killed and the rates of hepatic cholesterol synthesis and levels of hepatic esterified cholesterol were measured along with biliary lipid concentrations. Despite a 1000-fold variation in the rate of hepatic cholesterogenesis and a 100-fold variation in the levels of cholesteryl esters, the output and molar percentage of cholesterol in bile remained essentially constant with the exception of an approximate doubling in the output of cholesterol, as well as of bile acid and phospholipid in those animals fed bile acid. However, in this latter group the molar percentage of each component was unchanged. The administration of a bolus of chylomicrons did not alter output or molar percentage of cholesterol. Total biliary diversion for 36 hr and bile acid infusion were used to markedly vary the rate of biliary bile acid output. Cholesterol and phospholipid output remained tightly coupled to bile acid output over almost a 40-fold range. In other experiments it was shown that biliary cholesterol output could be driven by bile acid infusion to a similar extent in rats in which the rate of hepatic cholesterogenesis had been varied over a 26-fold range. It was concluded that the rate of hepatic cholesterol synthesis, the level of hepatic cholesteryl esters, and the amount of cholesterol absorbed from the diet play no role in determining the rate of biliary cholesterol secretion, at least in this species.-Turley, S. D., and J. M. Dietschy. Regulation of biliary cholesterol output in the rat: dissociation from the rate of hepatic cholesterol synthesis, the size of the hepatic cholesteryl ester pool, and the hepatic uptake of chylomicron cholesterol.

Animals↗
PubMed1978

On the mechanism for the regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, of cholesterol 7alpha-hydroxylase and of acyl-coenzyme A:cholesterol acyltransferase by free cholesterol.

The administration of mevalonic acid to rats by intravenous injection resulted in a dose- and time-dependent increase in the activity of cholesterol 7alpha-hydroxylase in the liver microsomal fraction, a decrease in the microsomal activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and no significant change in the activity of acyl-coenzyme A:cholesterol acyltransferase or in the concentration of free and of esterified cholesterol in the liver microsomal fraction. However, the increased hepatic cholesterogenesis that follows the injection of mevalonic acid resulted in an increase of the size of the intracellular pool of cholesterol that is in the environment of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and acts as substrate for cholesterol 7alpha-hydroxylase. The administration of mevalonic acid to rats by stomach tube resulted in an increase in the activity of cholesterol 7alpha-hydroxylase and of acyl-coenzyme A:cholesterol acyltransferase and in the concentration of cholesterol esters in the liver microsomal fraction, while there was a considerable decrease in the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase.

Acyltransferases↗
PubMed1977

Amperometric determination of total cholesterol in serum, with use of immobilized cholesterol ester hydrolase and cholesterol oxidase.

We describe an electrochemical method for simple, rapid, and economical assay of total serum cholesterol with use of immobilized cholesterol esterase (EC 3.1.1.13) and cholesterol oxidase (EC 1.1.3.6). A rotating porous cell was specially designed to hold the immobilized enzymes firmly and to allow the reaction mixture to pass through the enzyme layer easily, thus catalyzing the enzymatic transformation quickly. Hydrogen peroxide resulting from a catalytic reactions was measured amperometrically at +0.60 V cs. a standard calomel electrode. The calibration curve for total serum cholesterol was linear from 0 to 5.00 g/liter. The method is specific, precise, and inexpensive. Our results correlate well with those obtained by the method of Abell et al. [Stand. Methods Clin. Chem. 2, 26 (1958)], the correlation coefficient being 0.992. Ascorbic acid or bilirubin in concentrations up to 700 mg/liter do not interfere. The immobilized enzymes are stable, and the same immobilized-enzyme stirrer can be used for at least 200 accurate, reproducible assays.

Carboxylic Ester Hydrolases↗
PubMed1976

Polarographic method for rapid microdetermination of cholesterol with cholesterol esterase and cholesterol oxidase.

Cholesterol concentrations in serum are enzymatically determined rapidly by use of a polarographic oxygen analyzer with a circuit modified to record simultaneously the amount and rate of oxygen consumption. The final assay system, assessed from the oxygen consumption value that we found to be optimum, consists of 1 ml of sodium phosphate buffer (0.6 mol/liter, pH 7.0) containing NaN3 (10 mg/liter), Triton X-100 surfactant (10 ml/liter), 0.4 U of cholesterol ester hydrolase, and 0.6 U of cholesterol oxidase. Oxygen consumption and cholesterol concentration are linearly related to 8.0 g/liter, and only 10 mul of serum is required. Replicate analyses of pooled serum by the present method demonstrated the following inter-run precision: mean = 1731 mg/liter, SD = 22.3 mg/liter, CV = 1.3%. Bilirubin and ascorbic acid were without effect on the present method, unlike the enzymatic colorimetric methods.

Carboxylic Ester Hydrolases↗
PubMed1978

Multicompartmental analysis of cholesterol metabolism in man. Characterization of the hepatic bile acid and biliary cholesterol precursor sites.

The present report has presented the first clear evidence in man for the existence of specific hepatic cholesterol precursor sites associated with the formation and secretion of bile acids and biliary cholesterol. These hepatic compartments derive virtually all their cholesterol from newly synthesized and lipoprotein free cholesterol. The model which is presented was formulated on current concepts of cholesterol metabolism in man and is concerned, at this initial stage, with the elucidation of the bile acid and biliary cholesterol compartments. The complexity of cholesterol metabolism in man necessitated an initial approach that would minimize the number of inputs of cholesterol into the system, allow for the sampling of several cholesterol compartments, and permit the simultaneous labeling of newly synthesized cholesterol and preformed cholesterol. To achieve these objectives, we studied the patient with a total bile fistula. Six patients were administered simultaneously pulse injections of labeled mevalonic acid and [(14)C]cholesterol. The qualitative features of the specific activity time course curves after labeled mevalonic acid revealed no precursor-product relationship between bile acid, biliary cholesterol, and plasma free cholesterol. The peak specific activity of the bile acids was reached in approximately 100 min and was higher than the biliary cholesterol, which was higher than the plasma free cholesterol. The plasma free cholesterol specific activity became higher than the other lipids after 12 h and remained higher throughout the period of study. Similar related observations were made with [(14)C]cholesterol. The data were then subjected to simulation analysis and modeling using the SAAM-27 computer program. Computer least-square fits of the data were obtained after the model was evolved. During the model development, the least number of compartments and transport pathways were introduced consistent with a good fit of the data. Of particular importance was the constraint that the model fit the data obtained from both [(14)C]cholesterol and labeled mevalonic acid. The same parameter values were used to fit the data from both tracers. The fluxes arrived at in the model indicate that 31% and 20%, respectively, of the cholesterol input into the bile acid and biliary cholesterol precursor sites were derived directly from the newly synthesized hepatic cholesterol. The remainder had its origin predominantly from lipoprotein free cholesterol. Plasma esterified cholesterol (as free) made a small contribution (11%) to the bile acid compartment. Similarly, 10% of the biliary cholesterol arose from an unknown hepatic site. The present report has provided the basis for a new procedure for studying in vivo cholesterol metabolism in man. Examination of the derived cholesterol flux rates between the compartments suggests the presence of an important mechanism regulating the partitioning of lipoprotein free cholesterol between the bile acid and biliary cholesterol precursor sites. Aberrations in the proportioning of precursor cholesterol between these sites could be a causative factor precipitating the excessive secretion of biliary cholesterol and the production of lithogenic bile.

Aged↗
PubMedDate not supplied

Relationships between plasma lipoprotein cholesterol concentrations and the pool size and metabolism of cholesterol in man.

The plasma concentration of unesterified and esterified cholesterol within very low density (VLDL), low density (LDL) and high density (HDL) lipoproteins have been examined in relation to the metabolism and pool size of cholesterol in normal and hyperlipidaemic subjects. Cholesterol metabolism was assessed as faecal endogenous neutral and acidic steroid excretion, a 2-pool model of cholesterol turnover, and in vitro plasma cholesterol esterifying activity. VLDL total cholesterol (TC) concentration was positively correlated with cholesterol turnover, endogenous neutral steroid excretion, bile acid excretion and the absolute rate of plasma cholestrol esterification. The correlations with cholesterol turnover and neutral steroid excretion, but not that with bile acid excretion, remained significant when these were corrected for their relationships to body weight. LDL-TC was negatively correlated with the fractional rate of plasma cholesterol esterification and, in subjects with primary type IIa hyperlipoproteinaemia, also with the rate constant for cholesterol elimination from the rapidly exchanging cholesterol pool. No correlation was found between LDL-TC concentration and bile acid excretion. HDL-TC concentration was negatively correlated with both the rapidly and slowly exchanging pools of tissue cholesterol, after correction for their relationships to body weight and adiposity. In contrast, cholesterol pool sizes were not correlated with the concentration of VLDL or LDL-TC; nor was there any relationship to plasma cholesterol esterifying activity. No correlation was found between the relative proportions of unesterified cholesterol within any lipoprotein fraction and either the pool size or metabolism of cholesterol. These findings accord with previous reports of enhanced cholesterol metabolism in subjects with elevated VLDL concentrations and of impaired plasma LDL and cholesterol clearance in patients with primary type IIa hyperlipoproteinaemia. The demonstration that HDL-TC concentration is negatively correlated with body cholesterol pool size supports in vitro evidence for a role of HDL IN TISSUE CHOLESTEROL CLEARENCE.

Adolescent↗
PubMed1978

Cholesterol absorption and steroid excretion in cholesterol-fed guinea pigs.

Cholesterol absorption was studied in groups of guinea pigs fed diets containing 0, 0.1%, or 1% cholesterol. A similar proportion of tracer cholesterol was absorbed regardless of the cholesterol content of the diet. Furthermore, the proportion of tracer cholesterol absorbed by individual animals did not change when the cholesterol-free diet was changed to one containing 1% cholesterol. Cholesterol absorption was also measured in hyporesponding guinea pigs. These guinea pigs had been fed 1% cholesterol-containing diets for nearly a year with minimal pathological effects. These hyporesponders had a decreased intestinal transit time, which enabled them to decrease the fractional absorption of cholesterol below the levels seen in the controls, and to absorb less cholesterol/kg body weight than the hyperresponders. Excretion of total and of neutral steroids was measured in guinea pigs fed 0 or 1% cholesterol-containing diets. The 1% cholesterol-fed guinea pigs increased the excretion of steroids 3-fold over control levels. However, they absorbed more dietary cholesterol than they excreted in any form. It seems, therefore, that a major cause of the cholesterol pool expansion in the guinea pig is its inability to limit absorption of dietary cholesterol in conjunction with its inability to sufficiently increase excretion of steroids.

Aging↗
PubMed1978

Cholesterol from serum and cholesterol-phospholipid dispersions by isolated rat hepatocytes in vitro.

The rate of uptake of cholesterol by isolated rat hepatocytes from incubation medium containing rat serum was low and did not increase by the prolongation of incubation time up to 2 hr at 4 degree. However, the hepatocytes took up cholesterol very actively at 37.5 degree from serum as well as from a cholesterol-phospholipid dispersion. The cholesterol uptake by the cells from liposomes increased linearly with the increase of the cholesterol concentration of liposomes, but that from serum reached the maximum at about 1.5 mu mol/ml cholesterol and remained at a plateau level at higher concentrations. Cholesterol was transfered from every class of serum lipoprotein, although the uptake ratio was the highest from the LDL fraction. As the lipoprotein concentration was increased, the uptake ratio decreased in the same way as that observed in the incubation with whole serum. The concentration of labeled ester cholesterol in the medium decreased more rapidly than free cholesterol during incubation. Cholesterol in the hepatocytes, however, was found mainly as the free form, suggesting that ester cholesterol taken up by the cells was rapidly hydrolyzed. Cholesterol accumulation was not observed in hepatocytes incubated in medium containing serum, but their cholesterol content was increased after the incubation in medium with liposomes of high cholesterol concentration. Therefore the uptake of cholesterol by hepatocytes from serum lipoproteins is probably carried out by a process different from that of uptake from liposomes which is considered to be a physicochemical phenomenon.

Animals↗
PubMed1978

Stimulation of esterified cholesterol accumulation in tissue culture cells exposed to high density lipoproteins enriched in free cholesterol.

Human high density lipoprotein enriched in free cholesterol was obtained by exposing the lipoprotein to lipid dispersions having a free cholesterol/lecithin molar ratio greater than two. The metabolism of cholesterol was studied in tissue culture cells exposed to normal and cholesterol-enriched lipoproteins. Incubation of Fu5-AH rat hepatoma cells in medium containing cholesterol-enriched lipoprotein resulted in the accumulation of cellular cholesterol whereas normal high density lipoprotein produced no change in cellular content. The accumulated sterol was recovered primarily as esterified cholesterol and was derived almost entirely from lipoprotein free cholesterol. The esterification of incorporated free cholesterol and the cellular cholesterol content were directly related to the molar ratio of free cholesterol to phospholipid in the lipoprotein and to the concentration of lipoprotein in the culture medium. Isotopic experiments utilizing lipoprotein labeled with 125I or [4-14C]cholesteryl oleate demonstrated that a large fraction of the cholesterol incorporated from lipoprotein enriched in free cholesterol occurred by mechanisms that did not result in lipoprotein internalization and degradation. The response of other tissue culture cells to cholesterol/phospholipid dispersions is presented. The data indicate that the lipid composition of a lipoprotein can regulate free cholesterol uptake and esterification as well as cellular cholesterol content.

Animals↗
PubMed1978

Effects of saturated and unsaturated fats given with and without dietary cholesterol on hepatic cholesterol synthesis and hepatic lipid metabolism.

Hepatic cholesterol synthesis was studied in rats after consuming diets of varying neutral lipid and cholesterol content. Cholesterol synthesis was evaluated by measuring 3-hydroxy-3-methylglutaryl-CoA reductase and by determining the rate of 3H-labeled sterol production from [3H]mevalonate. Results were correlated with sterol balance data and hepatic lipid content. Hepatic cholesterol synthesis was relatively great when cholesterol was excluded from the diet. The source of neutral dietary lipids, saturated vs. unsaturated, produced no change in hepatic sterol synthesis. Values for fecal sterol outputs and hepatic cholesterol levels were also similar in rats consuming either saturated or unsaturated fats. When 1% cholesterol was added to the diet, hepatic cholesterol synthesis was suppressed but the degree of suppression was greater in rats consuming unsaturated vs. saturated fats. This was associated with greater accumulation of cholesterol in livers from rats consuming unsaturates and a reduction in fecal neutral sterol output in this group as opposed to results from rats on saturated fats. Cholesterol consumption also altered the fatty acid composition of hepatic phospholipids producing decreases in the percentages of essential polyunsaturated fatty acids. It is concluded that dietary cholesterol alters cholesterol and fatty acid metabolism in the liver and that this effect is enhanced by dietary unsaturated fats.

Animals↗
PubMed1979

Regulation of body cholesterol pools. Influence of cholesterol input and excretion in an animal model.

Biliary cholesterol excretion closely parallels lecithin excretion in the rat and may be increased by feeding an excess of choline and decreased by choline deficiency. To determine the relative influence of cholesterol input and excretion on whole body cholesterol metabolism, we have measured by compartmental analysis rates of cholesterol transport and pool sizes when both input and choline-mediated biliary excretion were increased and diminished. In choline-deficient animals with impaired excretion, plasma cholesterol was reduced. However, in deficient animals more cholesterol was transported into the slowly exchanging pool to increase pool size, and, when input was increased (by addition of cholesterol to diet), the slowly exchanging pool was even more markedly enlarged. In contrast, when excess choline was fed, plasma cholesterol was increased but excretion so exceeded transport into the slowly exchanging pool that pool size was actually reduced. Furthermore, in choline-fed animals with unimpaired excretion, addition of cholesterol to the diet to increase input did not result in pool expansion. Thus, in this model, cholesterol excretion and tissue deposition were reciprocally related, and, regardless of plasma cholesterol concentration and cholesterol input, stores were found to increase only when biliary excretion was impaired.

Animals↗
PubMed1979

[Influence of phosphatidylcholine/cholesterol molar ratios in liposomes on cholesterol reactivity with cholesterol:oxygen oxidoreductase].

The reactivity of sonicated phosphatidylcholine-cholesterol liposomes with cholesterol : oxygene oxydoreductase, an enzyme which catalyses the oxidation of the 3 beta hydroxyl group of cholesterol to a ketone group, is compared with that of ternary system phosphatidylcholine-cholesterol-Thesit. Regardless to the phosphatidylcholines nature and the phosphatidylcholine/cholesterol molar ratio (R), the enzymatic oxidation rate of liposomal cholesterol is slower than when the reaction is developed in the present of Thesit, a surfactif agent which destroyes the lamellar particles. This is true whether Thesit is added during preparation of dispersions or during incubation with cholesterol oxydase. The enzymatic oxydation rate of cholesterol of ternary systems phosphatidylcholine-cholesterol-Thesit is independent of the (R) value and the phosphatidylcholine fatty acid unsaturation, whereas that of phosphatidylcholine-cholesterol dispersions depends on these two parameters. The reaction rate increases in the order: dipalmitoylphosphatidylcholine to yolk egg phosphatidylcholines, and dioleylphosphatidylcholine. The optimal conditions for cholesterol oxidation were found to be R = 0.5. This result is not affected by the phosphatidylcholines nature. In order to explain these data, various hypotheses are considered. In particular, the weak liposomal cholesterol reactivity with cholesterol oxidase could result from an inhibitory effect on the enzyme-substrate combination due to the polar phosphorylcholine groups.

3-Hydroxysteroid Dehydrogenases↗
PubMed1978

The influence of a wide range of absorbed cholesterol on plasma cholesterol levels in man.

The influence of absorbed dietary cholesterol on plasma cholesterol concentration was studied in two populations, one Seventh Day Adventist (SDA) vegetarian and one nonvegetarian, representing a broad range of plasma cholesterol values and dietary cholesterol intakes. As a group, the SDA vegetarians had significantly lower levels of plasma cholesterol and triglycerides than did the nonvegetarians. This hypolipidemic pattern in the SDA vegetarians was apparently closely related to dietary habits, sinceanother group of SDA who were nonvegetarian had significantly higher plasma cholesterol and triglyceride levels than their vegetarian counterparts. Both the dietary intake of cholesterol and the percentage absorption of cholesterol were lower in vegetarians than in nonvegetarians. The mass of cholesterol absorbed increased linearly with the mass of cholesterol ingested in all groups, but no relationship could be demonstrated between absorbed cholesterol and plasma cholesterol concentration.

Absorption↗
PubMed1978

Diet and sire effects on serum cholesterol and cholesterol absorption in infant baboons (Papio cynocephalus).

One hundred three baboon infants, the progeny of an equal number of dams and seven sires, were breast fed or were fed prepared formulas containing 1.2, 29, or 61 mg/dl cholesterol for 14 weeks. We measured serum cholesterol and triglyceride concentrations at birth and at 3-week intervals, and cholesterol absorption at 12 weeks. Dietary cholesterol had a significant effect on serum cholesterol concentration at 12 weeks and on cholesterol absorption, but did not affect weight or serum triglyceride concentration. Sire had a significant effect on serum cholesterol concentration at birth and at 12 weeks, but the effect at birth did not predict the effect at 12 weeks. Sire did not affect cholesterol absorption, serum triglyceride concentration, or weight at 12 weeks. The sire effect on serum cholesterol concentration in infancy is not mediated by control of cholesterol absorption. Males weighed more than females at 12 weeks, but sex did not affect serum cholesterol concentration, triglyceride concentration, or cholesterol absorption.

Age Factors↗
PubMed1975

The effect of dietary rape-seed oil on cholesterol-ester metabolism and cholesterol-ester-hydrolase activity in the rat adrenal.

The effects of stock diet and stock diet supplemented by olive oil and rape seed on rat adrenal cholesterol ester metabolism have been studied. Rats fed rape seed oil failed to gain weight at the same rate as rats fed olive oil. A prominent feature of the rats fed rape seed oil was an accumulation of high concentrations of cholesterol erucate in the adrenal lipid droplets. When these rats were subjected to an ether stress no percentage decrease in the amount of cholesterol erucate was observed. Adrenal cholesterol ester hydrolase activity was higher in rats fed the olive oil and rape seed oil diets than rats fed the stock diet. In rats fed stock or olive oil diets, a ten-minute ether anaesthesia stress resulted in a two-fold increase in activity of adrenal cholesterol ester hydrolase. Cofactor addition of ATP, cyclic AMP and MgCl-2 in vitro resulted in a stimulation of cholesterol ester hydrolase to a similar activity in both quiescent and ether-stressed rats. By contrast rats fed the rape seed oil diet gave no significant stimulation of cholesterol ester hydrolase activity when given an ether stress or when cofactors were added in vitro. Cholesterol erucate was hydrolysed at only 25% to 30% of the rate of cholesterol oleate in vitro in all groups of animals. Oleic acid added in vitro gave an inhibition of cholesterol ester hydrolase activity in rats fed stock diet while erucic acid activated the enzyme. The accumulation of cholesterol erucate in the adrenal when rats are fed rape seed oil could be due to the reduced ability of cholesterol ester hydrolase to hydrolyse this ester.

Adenosine Triphosphate↗