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PubMed1977

Effect of type of dietary fat and cholesterol on cholesterol absorption rate in squirrel monkeys.

To explore the effect of the type of dietary fat and the level of cholesterol on the rate of cholesterol absorption, 13 different male squirrel monkeys were used for 39 different tests. The plasma isotope ratio technique of Zilversmit, which involved the injection of 3H-cholesterol and gastric intubation of 14C-cholesterol, was shown to give reproducible results which compared well with those based on a method involving labeled beta-sitosterol. The percentages of ingested cholesterol that were absorbed showed considerable variation among individuals, but were relatively constant in the same animal. Safflower oil, a highly unsaturated fat, promoted a higher rate of cholesterol absorption than butter, regardless of the level of dietary cholesterol. The rate of cholesterol absorption was a constant percentage of that fed regardless of the absolute level of cholesterol in the habitual diet or the test meal (up to 218 mg or 5+ mg/kcal). Even at low levels of dietary cholesterol the percent absorption is greater in squirrel monkeys than in man.

Animals↗
PubMed1975

Effect of cholesterol content on some physical and functional properties of mitochondria isolated from adult rat liver, fetal liver, cholesterol-enriched liver and hepatomas AH-130, 3924A and 5123.

The cholesterol to phospholipid ratio in mitochondria from hepatomas AH-130, 3924A and 5123 is higher than in the particles isolated from adult or fetal rat livers. Nearly all the cholesterol of hepatoma mitochondria is located in membranes. As in liver mitochondria, in the particles isolated from hepatoma AH-130 there is more cholesterol in the outer than in the inner membrane. In mitochondria from cholesterol-enriched liver and hepatomas, there occurs a decrease in extent of hypoosmotic and phosphate-induced swelling and a decrease of conformational changes linked to energy states. The phenomenon is more marked in particles which exhibit higher cholesterol to phospholipid ratios. A statistically significant negative correlation exists between the cholesterol to phospholipid ratio and extent of volume or conformational changes. No significant modifications of these parameters were found in fetal liver mitochondria. Cholesterol content does not influence K+ uptake by cholesterol-enriched or hepatoma mitochondria. Nor does cholesterol content affect the respiratory increment related to this uptake. As a consequence of K+ uptake, total mitochondrial water exchangeable with tritiated water rises 20% while sucrose-impermeable water rises 42-48% in both adult rat liver and hepatoma AH-130 mitochondria. Absorbance changes linked to ion uptake do not correspond merely to variations in mitochondrial water content. Water content is apparently not influenced by the cholesterol to phospholipid ratio. However, the ratio is significantly correlated to both extent and initial rate of absorbance decrease of mitochondrial suspensions during K+ uptake. The higher the ratio, the lower the extent and initial rate of absorbance decrease.

Animals↗
PubMed1978

Equilibrium studies of lecithin-cholesterol interactions. II. Phase relations in surface films: analysis of the "condensing" effect of cholesterol.

From measurements of the equilibrium spreading pressure pie for dispersions of lecithin--dimyristoyl (DML) or dioleoyl (DOL)--and cholesterol (CHOL) in water, we have deduced the phase relations in both the aqueous dispersions and the equilibrium surface films. At 29.5 degrees C, when the mole fraction of cholesterol in the dispersion chi(CHOL) is 0 chi(CHOL) less than chi(CHOL) less than 0.33, pie is constant and equal to the value for pure lecithin (DOL or DML). The phase rule predicts than two bulk lipid phases coexist; these are pure lecithin and lecithin:cholesterol 2:1 complex. The equilibrium surface film contants only lecithin and therefore lecithin and 2:1 complex are immiscible in surface films. When 0.33 less than chi/CHOL) less than 1.0, pie is also contant with a value intermediate between that for pure lecithin and cholesterol. In this range of lipid composition two bulk lipid phases also coexist: lecithin:cholesterol 2:1 complex and pure cholesterol. However, the equilibrium surface film contains only the 2:1 complex and, therefore, 2:1 complex is also immiscible with cholesterol in surface films. When pi less than pie, as in the case of spread films, we deduce that two surface phases may coexist; the composition of the phases will depend on chi(CHOL). When 0 less than chi(CHOL) less than 0.33, both lecithin and 2:1 complex coexist, and when 0.33 less than chi(CHOL) less than 1.0, 2:1 complex and cholesterol coexist. The "condensing" effect of cholesterol in lecithin surface films is reexamined. The effect is attributed to formation of the lecithin:cholesterol 2:1 complex and nonequilibrium conditions in the two-phase surface film.

Cholesterol↗
PubMed1979

Influence of hydrochlorothiazide on the plasma levels of triglycerides, total cholesterol and HDL-cholesterol in patients with essential hypertension.

The influence of hydrochlorothiazide (HCT) treatment on the plasma levels of triglycerides, total cholesterol and high density lipoprotein cholesterol (HDL-cholesterol) was studied in 10 patients with essential hypertension. After a placebo period of 4 weeks, 50 mg HCT twice daily was given for a period of 9 months, followed by a second placebo period of 4 weeks. Triglycerides, total cholesterol and HDL-cholesterol were determined at the end of both placebo periods and after 1, 3, 6 and 9 months of HCT. For the whole group, there were no significant changes in triglycerides or HDL-cholesterol, whereas total cholesterol significantly increased during HCT. In 6 patients, plasma triglycerides were higher during HCT as compared to both placebo periods. In only 4 patients did HDL-cholesterol increase during HCT. Changes in triglycerides, total cholesterol and HDL-cholesterol were not related and no correlation was found with changes in blood pressure, body weight or serum potassium. In conclusion, this study confirms a possible adverse effect of diuretic treatment on plasma lipids, which should be considered when determining therapeutic regimens for hypertension.

Adult↗
PubMed1979

Changes in cholesterol metabolism with dietary cholesterol in children with familial hypercholesterolaemia.

1. Possible defects in cholesterol metabolism were sought in children with familial hypercholesterolaemia. 2. In nine affected children (eight heterozygotes and one homozygote) and in five healthy children, cholesterol synthesis and bile acid synthesis were determined from the excretion of steroids in the faeces during a low cholesterol diet. Cholesterol synthesis of 10.1 +/- 4.4 mg day-1 kg-1 in the hypercholesterolaemic children was similar to that in these and other normal children. Mean bile acid synthesis of 4.0 +/- 2.1 mg day-1 kg-1 also resembled normal values though three severely affected heterozygotes excreted substantially less. 3. The response to 4 weeks' additional 450 mg of dietary cholesterol/day led to variable changes in the plasma cholesterol and in the sterol balance. On average the affected children showed a rise in plasma cholesterol which resembled that in healthy subjects. The sterol balance fell in most, suggesting a reduction in cholesterol synthesis, which is the normal response to dietary cholesterol. 4. The response to dietary cholesterol was therefore at least qualitatively similar in the hypercholesterolaemic children to that reported in healthy subjects.

Adolescent↗
PubMed1977

Effects of cholesterol feeding on synthesis and metabolism of cholesterol and bile acids in germfree rats.

The aim of the present investigation was to study the influence of cholesterol feeding on cholesterol synthesis and fecal excretion of bile acids in germfree rats. Four germfree rats were fed a basal diet containing 0.004% cholesterol and four germfree rats received the same diet supplemented with 0.4% cholesterol for 2 weeks. Cholesterol synthesis was studied by assaying the HMG CoA reductase activity in the liver microsomal fraction. Cholesterol feeding decreased the HMG CoA reductase activity from 28.5 +/- 6.6 (mean +/- SEM) to 9.1 +/- 0.7 pmol/mg protein per min. In another experiment four germfree rats received the basal diet and four germfree rats the cholesterol-enriched diet. After 6 weeks feces were collected in two 4-day pools for analysis of bile acids. The main fecal bile acids were cholic acid and beta-muricholic acid (a metabolite of chenodeoxycholic acid), comprising more than 95% of total bile acids. Cholic acid was increased from 3.9 +/- 0.2 to 9.9 +/- 1.2 mg/kg body weight per day and beta-muricholic acid from 6.6 +/- 0.5 to 21.8 +/- 3.1 mg/kg body weight per day. The percentage of cholic acid decreased from 37.1 +/- 1.1 to 31.2 +/- 1.0%. In conclusion, germfree rats like conventional rats have the ability to compensate for an increased input of dietary cholesterol by inhibition of cholesterol synthesis and stimulation of bile acid synthesis. The synthesis of chenodeoxycholic acid (implied from the fecal excretion of beta-muricholic acid) is stimulated to a greater extent than that of cholic acid.

Animals↗
PubMed1978

Models for lipid organization in cholesterol-phospholipid bilayers including cholesterol dimer formation.

Three new structural models, which account for abrupt changes in physical properties observed at several molar concentrations of cholesterol in phospholipid bilayers, are described. Cholesterol monomers, each surrounded by its own envelope of unshared acyl hydrocarbon chains of the phospholipid, can accommodate 22% cholesterol. Cholesterol dimers, each surrounded by its envelope of unshared acyl hydrocarbon chains, can accommodate 31% cholesterol. When surrounded by shared acyl hydrocarbon chains, cholesterol dimmers can accommodate about 47% cholesterol. At greater concentrations, cholesterol aggregation occurs, the system is unstable, and cholesterol forms a separate phase.

Chemical Phenomena↗
PubMed1977

Cholesterol-phosphatidylcholine dispersions as donors of cholesterol to Mycoplasma membranes.

Growing cells of sterol-requiring Mycoplasma hominis and sterol non-requiring Acholeplasma laidlawii were used to test the ability of cholesterol-dipalmitoyl phosphatidylcholine dispersions to serve as cholesterol donors to these organisms. Dispersions with high cholesterol to phosphatidylcholine ratios were more effective than dispersions with low cholesterol to phosphatidylcholine ratios in donating cholesterol to the membranes of both mycoplasmas and in promoting growth of the sterol-requiring species. M. hominis took up almost three times as much cholesterol as did A. laidlawii. In addition, significant quantities of the phosphatidylcholine component of the dispersions were found to be associated with M. hominis membranes as against none in the A. laidlawii membrane preparations. In all cases, the percentage of cholesterol taken up by M. hominis from the dispersions exceeded that of phosphatidylcholine by a factor of 3-5. These results were interpreted to suggest that all the cholesterol taken up by A. laidlawii is transferred from the dispersion to the membranes by a process which involves only a transient contact between the organisms and the lipid dispersions, whereas a certain amount of the cholesterol taken up by M. hominis may also be derived from lipid dispersions adhering to or fusing with the cell membranes.

Acholeplasma laidlawii↗
PubMed1976

Effect of cholesterol sulfate and sodium dodecyl sulfate on lecithin-cholesterol acyltransferase in human plasma.

The effects of cholesterol sulfate and sodium dodecyl sulfate (SDS) on the esterification of cholesterol in sonicated dispersions of lecithin-cholesterol mixtures by lecithin-cholesterol acyltransferase [EC 2.3.1.43] (LCAT) in human plasma were studied in vitro. The acyltransferase activity was inhibited at concentrations of cholesterol sulfate higher than 1 X 10(-4) M. This inhibition was not eliminated by the addition of bovine serum albumin or CaC12. On the contrary, the acyltransferase activity was stimulated at concentrations of SDS ranging from 1 X 10(-5) M to 1 X 10(-3) M, and maximum stimulation was obtained at 5 X 10(-4) M. The maximum stimulation disappeared on the addition of bovine serum albumin (30 mg per ml of incubation medium), 1 X 10(-3) M CaC12 or 1 X 10(-4) M cholesterol sulfate. On the other hand, the extent of inhibition of the acyltransferase by cholesterol sulfate was not affected by the amount of lecithin in the dispersion added as a substrate, but the maximum stimulation (5 X 10(-4) M SDS) of the acyltransferase was interfered with when a large amount of lecithin was present in the dispersion. In addition, the amount of SDS required for maximum cholesterol esterification was not affected by the amount of lecithin present in the dispersion. These results suggest that the action of cholesterol sulfate on the acyltransferase is different from that of SDS.

Acyltransferases↗
PubMed1979

Cholesterol metabolism in the liver and intestine of the chick: effect of dietary cholesterol, taurocholic acid and cholestyramine.

The effect of feeding cholesterol, taurocholic acid, or cholestyramine to chicks on cholesterogenesis from [1-14C] acetate in liver and intestine was determined in vitro using tissue slices, and in vivo by i.v. injection of [14C] acetate. The conversion of cholesterol to bile acids in liver in vivo was measured in the same treatments after i.v. injection of [3H] cholesterol. Hepatic cholesterogenesis in vitro and in vivo was depressed by dietary cholesterol and taurocholate and enhanced by cholestyramine. Intestinal cholesterogenesis in vivo was depressed only by taurocholate whereas ileal cholesterogenesis in vitro was reduced by dietary cholesterol. Conversion of cholesterol to bile acids was enhanced by dietary cholesterol and cholestyramine and depressed by taurocholate. Hepatic cholesterol metabolism in the chick appears to be regulated by mechanisms similar to those reported for other species.

Acetates↗
PubMed1979

Effect of enhancement of cholesterol degradation during neonatal life of guinea pig on its subsequent response to dietary cholesterol.

The effect of feeding cholestyramine to neonatal guinea pigs on their subsequent plasma cholesterol levels and response to dietary cholesterol were studied. Male neonatal guinea pigs were suckled for 6 days. One group was maintained on a 1.1% cholestyramine diet for 6 weeks and the control group weaned normally. Both groups of guinea pigs were then fed a standard diet of Guinea Pig Chow for 6 weeks. During the standard diet period bile acid and neutral sterol excretion rates were significantly higher in the group previously treated with cholestyramine than the control group despite the similarity in plasma cholesterol levels. When both groups of guinea pigs were subjected to a 0.5% cholesterol diet for 4 weeks, plasma cholesterol levels were significantly lower in the group previously treated with cholestyramine than the control group. The plasma cholesterol levels continued to be significantly lower in the group previously treated with cholestyramine after an additional four weeks on standard diet. These results suggest that stimulation of cholesterol catabolism in the neonatal period can influence the subsequent response to dietary cholesterol.

Animals↗
PubMed1979

Dependence of the effects of dietary cholesterol and experimental conditions on serum lipids in man. III. The effect on serum cholesterol of removal of eggs from the diet of free-living habitually egg-eating people.

Forty-four healthy free living volunteers were used to study the effect of the removal of eggs from a habitual egg-rich diet. The subjects, recruited by advertising, normally consumed at least 1 egg per day. During the 3-week experimental period they were not allowed to eat any eggs or products containing large amounts of eggs, except cakes and tarts. Elimination of eggs from a habitual egg-rich diet did result in a small but significant decrease in serum cholesterol levels in all subjects. No correlation could be demonstrated between changes in serum cholesterol levels and the age of the subjects and between changes in serum cholesterol levels and the numbers of eggs eaten per week before the experimental period. A significant negative correlation was found between changes in serum cholesterol levels and the Quételet index for obesity and between changes in serum cholesterol levels and the serum cholesterol levels before the experimental period. The results indicate that a very variable response is present in a human population toward dietary cholesterol. More research seems to be necessary to describe and select the population of hyperresponders, the subjects who are more sensitive to changes in dietary cholesterol, and the hyporesponders. The results moreover indicate that effects of dietary changes in a free-living population are much smaller than can be accomplished in populations under controlled conditions.

Adult↗
PubMed1979

Aqueous primary standard for use in measuring cholesterol by the cholesterol oxidase method.

An aqueous primary standard is needed for measuring cholesterol by enzymatic procedures. Sodium deoxycholate solubilizes cholesterol in water. Crystalline cholesterol (1.00, 3.00, 4.00, and 5.00 g/L), added to a solution containing 150 g of this compound per liter of a 9 g/L saline solution, was measured by a cholesterol oxidase procedure, with a centrifugal analyzer. The solubilizer did not interfere. When compared to an isopropanol-based commercial cholesterol standard, the cholesterol standard in solubilizer showed excellent correlation (r = 0.986; m = 0.989). Day-to-day variation for the mixture during nine days was small (CV, 2.9% at 100 g/L, 3.7% at 3.00 g/L, and 1.8% at 4.00 g/L). Linearity was maintained up to 5.00 g/L. The cholesterol concentration in four reference sera so analyzed maintained CV's of less than 4%. The viscosity of the mixture was similar to that of serum. The standard mixtures, stored at room temperature for 360 days, remained stable. The solubilized cholesterol standard is shown to be suitable for use in the enzymatic procedure.

3-Hydroxysteroid Dehydrogenases↗
PubMed1977

The reactivity of human erythrocyte membrane cholesterol with a cholesterol oxidase.

Cholesterol oxidase (EC 1.1.3.6, Brevibacterium sp.), which catalyzes the reaction: cholesterol + O2 leads to delta4-cholestenone + H2O2, has no effect on the cholesterol of intact (human) erythrocytes and of "resealed" ghosts, when it is present only outside these ghosts. The cholesterol of "leaky" ghosts, of "resealed" ghosts with enzyme trapped within, and of "inside-out" vesicles, was completely oxidized. This pattern indicates that the inner ((cytoplasmic) membrane surface must be exposed to the enzyme for the reaction to occur, and that outer surface cholesterol only becomes reactive after the membrane has been degraded by the oxidation of inner surface cholesterol. The enzymatic oxidations followed monotonic first-order kinetics, and hence gave no evidence to support the two states of cholesterol in the membrane that had been postulated earlier from studies on the plasma lipoprotein extraction of cholesterol from the membrane.

Brevibacterium↗
PubMed1979

The association of total cholesterol, triglycerides and plasma lipoprotein cholesterol levels in first degree relatives and spouse pairs.

HDL, VLDL, and LDL cholesterol as well as total cholesterol were measured in young adult offspring of Framingham Heart Study participants. Parental total cholesterol levels measured in the early 1950s were found to be significant predictors of present total cholesterol in the offspring. While both maternal and paternal cholesterol levels made an independent contribution to the prediction of the offspring's cholesterol, the mother's contribution was significantly greater than the father's for male offspring with a similar but less striking relationship for female offspring. The correlation for LDL cholesterol levels for siblings was higher than for HDL cholesterol or log VLDL choles terol. When adjustments were made for age, body weight, alcohol intake and cigarette smoking, slight reductions in the correlations were noted, but all adjusted correlations remained significantly different from zero. The spouse correlations for lipoproteins, however, did not differ from zero after adujustment. Since the significant association for lipoproteins in spouse pairs disappears on adjustment for correlates but the association for siblings does not, it is likely that the sibling lipoprotein associations result from either genetic or environmental factors shared early in life.

Adult↗
PubMed1977

High density lipoproteins (HDL) and physical activity: the influence of physical exercise, age and smoking on HDL-cholesterol and the HDL-/total cholesterol ratio.

220 trained men, examined the day before participation in a cross country ski-race, had significantly higher HDL-cholesterol and HDL-/total cholesterol ratio than untrained men, but did not differ signficantly from untrained women. HDL-cholesterol was significantly higher in skiers above 60 years than in skiers of younger age. Tobacco smokers ahd lower HDL-cholesterol and HDL-/total cholesterol ratio than non-smokers, but the differences were only significant in skiers, not in controls. HDL-cholesterol was positively correlated to total cholesterol in skiers. The HDL-cholesterol level may possibly contribute to the lower morbidity of CHD in men who are physically active during leisure time.

Adolescent↗