Increased Serum Cholesterol Levels Research Articles

Effect of combined clofibrate-cholestyramine treatment on serum and tissue cholesterol pools and on cholesterol synthesis in hypercholesterolemic swine

The effect of clofibrate on whole-body cholesterol synthesis was studied in cholestyramine-treated hypercholesterolemic male Yorkshire swine and swine with normocholesterolemia or mild hypercholesterolemia. Daily whole-body synthesis rates were calculated by methods developed for the non-steady-state condition using various parameters of cholesterol balance; dietary cholesterol intake, fecal excretion of steroids, and cholesterol retention or loss in the body. After 16 days of treatment, the cholestyramine group showed reductions in serum cholesterol level and carcass cholesterol concentration, and increases in fecal steroid excretion and whole-body cholesterol synthesis, as compared with pretreatment values. The group which received both cholestyramine and clofibrate showed the same changes in all parameters listed above, but showed a greater reduction in serum cholesterol levels and greater increases in fecal excretion and whole-body cholesterol synthesis as compared with the group receiving cholestyramine alone. Unfortunately for the therapeutic implications, the increased output of steroids resulting from treatment with the combination of the two drugs was largely offset by a corresponding increase in cholesterol synthesis. The increase in synthesis might have been caused by a direct effect of clofibrate on the biosynthetic process. However, it seemed more likely that the increased synthesis was secondary to the increased output of steroids. The effect of clofibrate alone in hypercholesterolemic swine treated for 64 days revealed restraint in increase of serum cholesterol levels as compared to untreated controls, and an increase in total steroid excretion. No reduction in the whole-body cholesterol synthesis was observed in the clofibrate-treated group. In the other experiment, clofibrate even under mildly hypercholesterolemic or normocholesterolemic conditions did not result in a reduction of whole-body cholesterol synthesis, although serum cholesterol levels were reduced under both conditions.

Relation of Serum Cholesterol to in vitro 7α-Dehydroxylation of Primary Bile Acids by Fecal Bacteria in Infants and Children

Fresh feces from 104 infants and children (aged 3 days to 16 years) were homogenized and incubated with labeled cholic or chenodeoxycholic acid. After 2 and/or 24 hours' incubation, the percentage of converted (mostly 7α-dehydroxylated) primary bile acids was measured, and the degree of conversion was correlated with serum cholesterol levels. It was found that stool homogenates of patients with low levels of serum cholesterol (< 160 mg/100 ml) converted labeled primary bile acids poorly or not at all, whereas in patients with higher serum cholesterol levels (> l60 mg/100 ml) the conversion process was markedly increased. Thus, highly significant correlations were found between serum cholesterol levels and the capability of the fecal bacterial flora to convert both primary bile acids "in vitro." The possibility is proposed that in man the relatively rapid progressive increase of serum cholesterol level following birth may be related to the colonization of the intestinal tract by 7α-dehydroxylating and/or bile acid degrading bacteria. It is suggested that the prevalence of these bacteria is subject to environmental effects, and it may be one of the important factors regulating cholesterol levels in man.

Stimulation of hepatic β-hydroxy-β-methylglutaryl coenzyme a reductase activity in allylamine-fed rats

Rats fed a diet containing 0.2% allylamine hydrochloride had a 5-fold higher level of hepatic β-hydroxy-β-methylglutaryl coenzyme A reductase activity than corresponding controls. Supplementation of the allylamine-containing diet with 10% egg yolk reduced this elevated level of reductase activity. In contrast to the marked rise in their liver enzyme activity, allylamine-fed rats had no increase in serum cholesterol levels.

Comparison of serum cholesterol values in amerindians from surinam with those of dutch controls

A description is given of a comparative study of serum cholesterol values in 250 Indians of the Trio and Wajana tribes in Surinam, and in a Dutch control group. From childhood on, these values are higher in the Dutch controls than in the Indians. No increase of serum cholesterol levels with increasing age is demonstrable in the Indians.

Effect of sodium hydrodextran sulfate on experimental arteriosclerosis in spontaneously hypertensive rats

In order to examine the effect of sodium hydrodextran sulfate (HDS) on experimental atherosclerosis spontaneously hypertensive rats (SHR) and normotensive Wistar rats (NR) were fed a high-fat diet with and without the drug. Blood samples were collected for 5 months to measure serum levels of cholesterol, triglyceride and clearing factor lipase activity. Effect of HDS on certain blood factors were as follows: 1) HDS inhibited the increase of serum cholesterol levels in rats. 2) HDS did not change the triglyceride concentration. 3) HDS elevated the clearing factor lipase activity. 4) A high-fat diet increased the intimal thickening of arteries in SHR. 5) Intimal thickening of arteries decreased slightly in the HDS treated group.

Influence of Strain Differences on Serum Cholesterol Levels in Rats

The purpose of this study was to clarify the relationship between rat strain and the serum cholesterol level.Wistar, Donryu and Sprague-Dawley strain rats of both sexes were divided into 2 groups and fed on the following two kinds of diet for 10 days; a standard diet not containing cholesterol and a cholesterol diet containing 1% cholesterol and 0.25% bile salts. After 10 days, the animals were fasted overnight and the serum total cholesterol level was measured.Wistar strain was very similar to the Donryu strain in respect of the serum cholesterol level. In both strains, serum cholesterol levels in rats placed on the standard diet were about 80mg/dl, regardless of sex. Dietary cholesterol caused a rather significant increase in serum cholesterol levels reaching 100-110mg/dl, regardless of strain or sex.Sprague-Dawley strain rats fed on the standard diet showed a higher serum cholesterol level (about 100mg/dl) than the Wistar or Donryu strains. When the Sprague-Dawley rats were placed on the cholesterol diet, a marked elevation in the serum cholesterol value was observed in the males (156mg/dl) and furthermore in the females (256mg/dl).Liver total cholesterol level of the Sprague-Dawley rats maintained on the cholesterol diet was also the highest among the three strains.

Diet-induced hypercholesterolemia in the chinchilla and rabbit

Male chinchillas develop a marked hypercholesterolemia when fed a diet containing 10.0% lard and 0.5% cholesterol by weight. A less striking yet significant increase in serum cholesterol levels also were observed in chinchillas fed a 10% lard containing diet. Chinchillas unlike the rabbits fed the same diet did not have aortic or severe coronary artery atherosclerosis. Lipoid deposits in the choroid plexus, hepatic fatty metamorphosis with fibrosis and adrenal cholesterolosis were seen in both rabbits and chinchillas fed the lard-cholesterol containing diet.

Long-term decay of serum cholesterol radioactivity: body cholesterol metabolism in normals and in patients with hyperlipoproteinemia and atherosclerosis.

After the intravenous injection of labeled cholesterol, the decay of specific radioactivity of total serum cholesterol was studied in 12 patients for 15-63 wk (average, 45 wk). In some, but not all of the patients studied, the slow slope of the decay curves suggested a deviation from monoexponential behavior, and the data of the slow period of the decay of specific activity were curve fitted by two exponentials. Six patients had serum lipid values regarded as normal and six had hyperlipoproteinemia. The data were analyzed by input-output analysis and yielded the following results. Values for the input rate of cholesterol (I(T)) (the sum of dietary and biosynthesized cholesterol) showed no difference between the normals and patients with hypercholesterolemia. The size of the rapidly miscible pool of cholesterol (M(a)) was significantly higher in the group of hypercholesterolemic patients partly due to increased serum cholesterol levels. The size of the total exchangeable body mass of cholesterol (M) was higher by an average of 49 g in the patients with hypercholesterolemia as compared to normals. The remaining exchangeable mass of cholesterol (M - M(a)) of the hypercholesterolemic subjects was higher by an average of 29 g as compared to normals. These differences were statistically significant.

Effect of neomycin on cholesterol levels and bile acid excretion in germfree and conventional rats

Germfree rats on either a 1 % cholesterol diet for 21 days or a 1 % cholesterol −0.1 % cholic acid diet for 17 days exhibited serum and liver cholesterol levels which were 50 % to 100 % higher than those of comparable conventional controls. Administration of neomycin to rats on a 1 % cholesterol −0.1 % cholic acid diet increased serum cholesterol levels by 100 % and liver cholesterol levels by 50 % in the conventional animals but was without effect on the high cholesterol levels of the germfree group. Neomycin did not affect the fecal bile acid or sterol output of germfree rats but significantly reduced the fecal bile acid loss of the conventional group.

Placental transfer of cholesterol-4-14C into rabbit and guinea pig fetus

A tracer dose of cholesterol-4-(14)C was given daily in the diet of six pregnant guinea pigs to establish an isotopic steady state. At the time of parturition, maternal and fetal blood and fetal tissues were collected and analyzed for cholesterol content and cholesterol specific activity. A comparison of these specific activities in neonatal and maternal serum indicated that about 22% of the fetal serum cholesterol was transferred from maternal blood. In the newborn, tissues generally had the same cholesterol specific activity as serum. Brain tissue was an exception in having a specific activity only 8.4% of that of serum. Dietary cholesterol did not increase serum cholesterol levels in the newborn but did increase the percentage of fetal cholesterol derived from the maternal circulation. The rapid transfer of cholesterol-4-(14)C across the placenta was indicated by the appearance of this isotope in the newborn 2 days after its administration to pregnant rabbits. A considerable amount of the cholesterol content of newborn guinea pigs and rabbits originated from the maternal blood.

Anti-hypercholesterolemic effect of dehydroepiandrosterone in rats.

SummaryDehydroepiandrosterone (DHA) and 3α-methoxy − 17α−methyl− 5α −androstane−17α−01 (SC-12790) were studied for their anti-hypercholesterolemic and thyromimetic activities. The following findings were established: 1. DHA (5 mg/kg/d per os for 10 days) was found to be an anti-hypercholesterolemic agent which prevented increase in the serum cholesterol level (SCL) of rats made hypercholesterolemic by propylthiouracil (PTU) treatment. It was also found that the same dose of DHA given over a period of 21 days prevented an increase in SCL in rats made hypercholesterolemic by combined PTU and cholesterol feeding. DHA, however, did not reduce the SCL of normal rats. 2. SC-12790, when given under the same experimental conditions as DHA, did not reduce the SCL of hypercholesterolemic rats. 3. DHA did not produce any change in thyroid weight as did exogenous TSH and T-3. It seems that the anti-hypercholesterolemic effect of DHA cannot be explained by a thyromimetic activity. These findings are of clinical import...

Effect of Dietary Fat, Protein and Cholesterol on Atherosclerosis in Swine

Three trials involving 48 pigs each were conducted to study the effects of high and low levels of energy intake from 2 fat sources (soybean oil versus tallow), protein level (18 versus 12%) and the addition of 1% cholesterol to the above fat sources, on serum cholesterol levels and the incidence of atherosclerotic lesions in the thoracic and abdominal aortas and coronary arteries. The feeding of diets containing tallow generally resulted in a trend toward higher serum cholesterol levels and increased incidence of lesions except in trial 1, where the coronary arteries of the pigs receiving the diets containing soybean oil had the greater incidence. Serum cholesterol levels were unaffected by the levels of energy intake. The effect of caloric intake on the incidence of lesions was inconsistent. The pigs fed the diets containing 12% protein had slightly elevated serum cholesterol levels as opposed to those fed the diets containing 18% protein. The effect of protein level on the incidence of lesions was inconsistent. Cholesterol addition to the diets significantly increased serum cholesterol levels and incidence of lesions as compared with that observed in the pigs on similar diets without cholesterol addition.

Dietary lipids and thrombosis: Factors in blood that account for increased “binding power” in rats fed thrombogenic diets

In previous studies with rats we observed that certain thrombogenic diets resulted in a stronger clot (greater binding power as measured in the thrombelastograph) and prolonged clot-lysis times as compared to simple stock diets. Furthermore, there was a close correlation between the plasma fibrinogen concentration and the binding power. In an attempt to investigate further the previously observed relationship between plasma fibrinogen and binding power, varying amounts of purified fibrinogen were added to plasma with normal fibrinogen levels, and the binding powers were measured in the thrombelastograph. It was found that the binding power was directly proportional to the fibrinogen concentration in the plasma. The experiment was carried out further to determine how early changes in various coagulation factors begin to take place after initiation of high-fat diets. Fibrinogen and prothrombin levels began to rise as early as within 1 week after the administration of high-fat diets. The changes were accompanied by a significant increase of serum cholesterol levels. By the 18th day prothrombin and fibrinogen concentrations doubled their control values, and the increase in serum cholesterol was more than tenfold.

Hypocholesteremic effect of phenoxybenzamine (dibenzyline), an adrenergic blocking agent. Experimental studies with monkeys and human volunteers.

The effect of an orally effective adrenergic blocking agent, Dibenzyline, on serum cholesterol levels was studied in human subjects and in monkeys on high-fat diets. In addition, the effect of the phenoxyethyl analogue of Dibenzyline, G-D 131, was also investigated in monkeys. The studies showed that the increase in serum cholesterol level brought about by a high-fat diet in monkeys could be considerably reduced by supplementation with Dibenzyline. This hypocholesteremic action was also observed with the analogue of Dibenzyline, G-D 131, which does not possess the adrenergic blocking property. It appears, therefore, that the hypocholesteremic action of Dibenzyline is independent of its adrenergic blocking activity. When a high-fat diet which also contained a high amount of cholesterol was used, Dibenzyline retarded the increase in serum cholesterol of monkeys for a considerable length of time. Administration of Dibenzyline, 10 mg. daily for 11 days, brought about a fall in serum cholesterol in two of the three human subjects and arrested the further increase in serum cholesterol in the third subject on a high-butterfat diet. All the subjects showed increased fecal elimination of cholic and dihydroxycholanic acids during the Dibenzyline-supplemented period, suggesting that the hypocholesteremic effect of the drug is at least partly mediated through increased elimination of cholesterol as bile acids.

Pigmy marmoset as an experimental animal.

The pigmy marmoset has been maintained under laboratory conditions for approximately (1/2) years. A synthetic diet has been prepared, which includes milk, eggs, and lard, which may cause fourfold increase in serum cholesterol levels. This species is proposed as an experimental subject for the study of aging and age-associated diseases.

Effects of chronic treatment with carbutamide on distribution and biosynthesis of fatty acids and cholesterol in obese-hyperglycemic mice.

Oral treatment with carbutamide (BZ-55) for 7 weeks (2.5 gm/kg of ground chow) left the food intake and rate of weight gain of obese-hyperglycemic mice and lean littermates unmodified as compared with untreated controls. Obese-hyperglycemic animals, after 49 days of treatment showed the usual distribution and rate of biosynthesis of fatty acids and cholesterol in the liver and carcass. Liver hypertrophy, marked increase in serum cholesterol levels and lack of improvement of the ‘diabetes’ were also observed in these animals. Lean littermates similarly treated showed no modification in the distribution of fatty acids and cholesterol and in the biosynthesis of fatty acids in the liver and carcass. An increase in hepatic cholesterologenesis, liver hypertrophy, some increase in serum cholesterol levels and a small but significant increase in the blood sugar levels were noticed.

Relationship of fluoride and dietary fats to serum cholesterol in rats.

SummarySerum cholesterol level was determined in 5 series of rats receiving either different fats in their diets or different fats plus fluoride to determine whether the use of fluoride is associated with an increased serum cholesterol level. After administration of 2 mg of fluoride daily throughout a 10-week period there was no significant change in serum cholesterol level of rats regardless of their dietary fat source or the presence of fluoride. Comparison of body weight gains of the various groups fails to suggest that any of the fats used resulted in increased fluoride toxicity.

The pathogenesis of hyperlipemia induced by means of surface-active agents. II. Failure of exchange of cholesterol between the plasma and the liver in rabbits given triton WR 1339.

Rabbits subjected to subtotal hepatectomy failed to develop increased serum cholesterol levels following parenteral injection of triton WR 1339, the finding indicating that the liver is essential for the establishment of the hypercholesterolemia induced by surface-active agents. The cholesterol content of the livers of rabbits rendered hyperlipemic by means of triton remained unchanged both during the rapid rise of the serum cholesterol levels and during the return to normal values. By contrast, the cholesterol content of the livers of rabbits fed cholesterol rose progressively over a period of 5 weeks, concommittant with the increase in serum cholesterol levels. The findings provide support for the hypothesis that surface-active agents bring about hyperlipemia by altering the circulating lipoproteins in some manner so that they are retained in the circulating body fluids.

The serum lipoprotein and cholesterol concentrations of Central and North Americans with different dietary habits

1. 1. The total cholesterol and beta-lipoprotein measurements of the blood sera of a group of rural Central American subjects subsisting on a largely vegetarian and very low fat diet have been compared with those of urban Guatemalan and North American subjects who habitually eat large amounts of fat. 2. 2. The rural Central American subjects, both male and female, were shown to have lower mean cholesterol levels at all ages studied than did the other groups. There was little evidence of the typical North American increase of serum cholesterol level with age among these Central Americans. There was no sex-determined difference of mean cholesterol levels by decade among the rural Central American subjects. The cholesterol levels of urban Guatemalans living in a good economic status were similar to those of North Americans. 3. 3. The serum lipoprotein differences observed among the groups were variable. They were only slightly and irregularly lower in the rural Central American males than in the North Americans and the beta-lipoproteins of the females of this group were frequently at higher levels than those of the North Americans. The urban Guatemalans showed lipoprotein levels as high or higher than those of the North American group. 4. 4. These cholesterol and lipoprotein level differences could not be explained by the greater leanness of the Central Americans although this factor could be shown to have a small effect. 5. 5. The greater leanness of the rural Guatemalan group taken with higher caloric consumption of that group suggests that the serum lipoprotein levels may be dependent upon the magnitude of energy turnover whereas the serum cholesterol levels are increased by energy accretion or fat deposition. 6. 6. The differences in dietary fat intake among the groups do not serve to explain the serum lipid differences because they do not permit an explanation of the dissociation of cholesterol and lipoprotein measurements which is unique in the rural Guatemalans. 7. 7. These Guatemalan populations appear to be a useful place to evaluate the relative importance of serum beta-lipoprotein and cholesterol levels in atherogenesis.