Hypercholesterolemic Response Research Articles

Influence of Dietary Fat and Cholesterol on Milk Lipids and on Cholesterol Metabolism in the Rat

The experimental basis for a hypothesis of Reiser and Sidelman (J. Nutr. 102: 1009, 1972) that cholesterol intake early in life is inversely related to an animal's subsequent hypercholesterolemic response to dietary cholesterol was tested. Female rats (seven per group) were fed either a stock diet (group 1), a semisynthetic diet with 15% lard (group 2) or the semisynthetic diet with 15% lard and 1.5% cholesterol (group 3) from day 18 of gestation and during lactation. Plasma cholesterol concentration during lactation was significantly higher in group 3 dams, but there were no significant effects of maternal diet on milk cholesterol or triglyceride concentration. Pups had access to the dams' diets until weaning at 30 days of age. Plasma and liver cholesterol concentrations at weaning were significantly higher in pups from group 3 dams than in those from the other groups. All pups were fed a semisynthetic diet containing 10% lard and 0.5% cholesterol from 60 to 161 days of age. Plasma cholesterol concentration during this time was significantly lower in male pups from group 1 dams than in those from other dams. Plasma cholesterol concentration in female pups showed a similar trend and was, on the average, significantly higher in females than males. Pup liver cholesterol concentration after weaning was not significantly influenced by maternal diet. Thus, these data do not support the hypothesis that cholesterol intake in early life is inversely correlated with subsequent response to dietary induced hypercholesterolemia.dietary cholesterol hypercholesterolemia

Effect of sucrose polyester on plasma lipids and cholesterol absorption in African green monkeys with variable hypercholesterolemic response to dietary cholesterol

The effect of sucrose polyester (SPE), a nonabsorbable fat, on plasma lipids and cholesterol absorption was studied in 29 adult male African green monkeys whose plasma cholesterol concentrations ranged from 133 to 358 mg/dl while consuming a diet containing 0.36 mg cholesterol/kcal. SPE was added to this diet at concentrations equivalent to doses for human beings of 15, 30, and 45 g/day. All 29 animals were fed either no SPE or one of the three concentrations of SPE for 2-mo intervals in a Latin square experimental design which ultimately allowed each animal to receive all dietary treatments. The lowest concentration of SPE reduced absorption of dietary cholesterol in all animals by an average of 16%. Increasing the concentration of SPE did not further decrease cholesterol absorption. Plasma cholesterol concentrations, however, were reduced by SPE only in the most hypercholesterolemic animals. The plasma cholesterol lowering effect was progressively less in animals that were less responsive to dietary cholesterol, such that in animals with plasma cholesterol concentrations less than 200 mg/dl there was no effect of SPE. The cholesterol lowering effect of SPE was due entirely to a lowering in LDL, with no effect on HDL cholesterol or triglycerides. Animals with the greatest plasma cholesterol response (hyperresponders) absorbed a significantly higher percentage of dietary cholesterol than did hyporesponders (56% vs. 37%). When cholesterol absorption was decreased in hyperresponders by SPE to levels equivalent to hyporesponders, the hyperresponders still maintained higher plasma cholesterol concentrations. Thus, the difference in cholesterol absorption appears to only partially explain the individuality in plasma cholesterol response to dietary cholesterol. These results also suggest that SPE may be a particularly useful drug in lowering plasma cholesterol concentrations in individuals that are hyperresponsive to dietary cholesterol.

Feedback regulation of cholesterol biosynthesis in rhesus monkeys with variable hypercholesterolemic response to dietary cholesterol

To test the hypothesis that high-responding rhesus monkeys should have a greater degree of feedback inhibition of hepatic cholesterol biosynthesis than the low-responding monkeys because the former group absorbs a higher percentage of cholesterol than the later group, we determined the relative rates of cholesterol biosynthesis by measuring plasma desmosterol levels while feeding triparanol along with diets high and low in cholesterol and with or without 2% plant sterols. The build-up of plasma desmosterol was more rapid in low-responders than in high-responders on all diets; the difference was significant only on diets low in plant sterols. In both groups, adding plant sterols to either diet increased the initial slope of plasma desmosterol build-up (significant only for high cholesterol diet). The mean percent cholesterol absorption in high-responders was significantly higher than in low-responders on high and low cholesterol diets with low levels of plant sterols. On adding 2% plant sterols to both diets, the percent cholesterol absorption decreased significantly and became essentially the same in both groups. Triparanol feeding decreased plasma cholesterol significantly in both groups on both diets; the decrease in the low-responders was smaller than in high-responders. Addition of plant sterols to either diet also reduced plasma cholesterol in both groups, but the decrease was significant only in the high-responders on high cholesterol diet. The study demonstrates that high-responders have a greater degree of feedback inhibition of cholesterol biosynthesis than low-responders probably because of higher absorption of cholesterol. The results also indicate that both endogenous and exogenous cholesterol are effective mediators of the feedback inhibition mechanism.

The feect of neutrotensin on the plasma cholesterol levels in the rat

The effect of the hypothalamic tridecapeptide neurotensin (NT) on the plasma cholesterol levels was studied in the rat. 15 min after the intravenous administration of 1.25 pmol/100 g body weight NT, the concentration of the total plasma cholesterol was increased about 25% above the control values (P<0.001) and remained at about the same level 30 min after the injection. The hypercholesterolemic response to the intravenous administration of NT increased dose dependently (12.5 and 125 pmol). Adrenalectomy and hypophysectomy did not modify the hypercholesterolemic effect of NT. The data suggest that NT have a role in cholesterol transport.

Dietary fiber and cholesterol metabolism in rabbits and rats ,

Rabbits fed semipurified diets have elevated plasma cholesterol levels, and they oxidize [26-14C]cholesterol to expired 14CO2 more slowly than rabbits on a natural ingredient diet. Addition of several different types of fibrous material to a semipurified diet failed to prevent the hypercholesterolemic response. Rats on semipurified diets also oxidized [26-14C]cholesterol more slowly and tended to have somewhat higher plasma cholesterol levels than rats on commercial feed. Cholesterol oxidation was not stimulated by addition of fibrous materials to the semipurified diet, but rats fed a semipurified diet containing raw potato starch oxidized cholesterol at a rate comparable to that of rats on commercial diet. Raw potato starch was poorly digested by the rats. Cooked potato starch was well digested and failed to stimulate the rate of oxidation of cholesterol. A semipurified diet containing raw potato starch did not produce a hypercholesterolemic response in rabbits, even though the raw starch was well digested.

Plasma cholesterol levels in rabbits fed low fat, cholesterol-free, semipurified diets: effects of dietary proteins, protein hydrolysates and amino acid mixtures

Rabbits become hypercholesterolemic when fed a low fat, cholesterol-free, semisynthetic diet containing casein as the dietary protein. This did not occur when the casein was replaced by soy protein isolate or any one of seven other plant protein preparations. Doubling the amounts of either the casein or soy protein isolate from 25 to 50% by weight of the diet, made no significant difference to their effects on plasma cholesterol. Soy protein isolate was effective in counteracting the hypercholesterolemic response to casein when mixtures of the two proteins were fed. There appeared to be no relationship between body weight gains and plasma cholesterol levels in rabbits fed the different diets. Animals fed the higher level of casein failed to gain weight, whereas growth was not significantly impaired by doubling the level of soy protein isolate in the diet. Better growth was obtained with mixtures of casein and soy protein isolate than with either protein alone. An enzymatic hydrolysate of casein or a mixture of L-amino acids equivalent to casein gave elevated plasma cholesterol levels similar to those obtained with the intact protein. Plasma cholesterol levels remained low in rabbits fed an enzymatic digest of soy protein. A moderate, but not significant, increase in plasma cholesterol was observed when a mixture of L-amino acids equivalent to soy protein isolate was fed. The results of these experiments indicate that the level of plasma cholesterol can be influenced by the amino acids supplied in the diet.

Plasma cholesterol levels in rabbits fed low fat, low cholesterol diets Effects of dietary proteins, carbohydrates and fibre from different sources

Rabbits become hypercholesterolemic when transferred from commercial feed to a low fat, cholesterol-free semisynthetic diet. The role of different dietary components in mediating this effect was investigated by varying the composition of the semisynthetic diet and of the commercial feed. Addition of alfalfa to the semisynthetic diet prevented the normal hypercholesterolemic response, but other plant products, including several with high fibre content, were ineffective. Increasing the content of powdered cellulose appeared to enhance the response. A commercially formulated diet in which the alfalfa and soybean meal components were replaced by ground corn and oats did not produce a significant elevation of plasma cholesterol. Substitution of different sugars or starches for the dextrose in the semisynthetic diet gave variable results, but of those tested, only potato starch prevented the hypercholesterolemia. The type of protein used in the semisynthetic diet had a marked influence on the level of plasma cholesterol. Semisynthetic diets containing proteins from animal sources gave higher plasma cholesterol levels than those containing proteins from plant sources. Very low levels were obtained with a low choline semisynthetic diet containing soy protein isolate, and supplementation with choline and methionine only raised the level to that normally obtained with commercial feed. Replacement of the salt mixture in the semisynthetic diet by one specially recommended for rabbits made no significant difference to the hypercholesterolemic response. Prevention of coprophagy did not significantly affect plasma cholesterol levels in rabbits on either commercial or semisynthetic diets. Growth performance was generally better on commercial feed than on semisynthetic diets but there was no direct correlation between weight gain and level of plasma cholesterol in rabbits on the different semisynthetic diets.

Pathogenesis of acute arterial fat deposition in spontaneously hypertensive rats.

The selectively-bred substrains of spontaneously hypertensive rats with a greater vulnerability to vascular lesions rapidly developed arterial fat deposition within 1 or 2 weeks as well as a greater hypercholesterolemic response when fed on high fat cholesterol diet including 20% of suet, 5% of cholesterol and 2% of cholic acid. The ring-like arterial fat deposition at the branches of superior mesenteric arteries and cerebrobasal arteries, which was found to be good indices for the deposition of intrarenal or coronary arteries, was not observed in normotensive rats fed on high fat cholesterol diet for 3 months, greatly delayed in SHR under antihypertensive treatment and accelerated by 1% salt loading in drinking water. The horseradish peroxidase infused intravenously 1 to 4 hours before sacrifice leaked in ring-like forms which corresponded to the fat deposit in mesenteric arteries. The incorporation of 3H-proline infused 4 hours before sacrifice was enhanced in the mesenteric arteries with the fat deposition. These results clearly indicated that hypertension was a great contributory factor to rapid arterial fat deposition, which was caused by an increased vascular permeability and enhanced the arterial collagen formation, the initiation process of arterio- or atherosclerosis.

GROUP ISOLATION AND ATHEROSCLEROSIS IN CHOLESTEROL-FED COCKERELS.

Group isolation, a highly unnatural environmental situation in cockerels, increases atherogenesis and decreases regression of previously induced atherosclerosis. This alteration occurs despite the absence of change in the hypercholesterolemic response to the diet in the induction experiments. It is accompanied by a reduction in weight gain despite food intake similar to the controls. Disturbing the social order by altering the pecking order in flocks of cockerels on a cholesterol-oil containing diet does not alter hypercholesterolemia and atherogenesis. However, it leads to increase in sex characteristics. Physical activity, with or without alterations in pecking order, causes a reduced weight gain even when food intakes are not altered. It is concluded that environmental factors can and do influence atherosclerosis. The types of environmental change which can produce this effect and the exact mechanisms involved require further study.