Turnover of low density lipoproteins during inhibition of cholesterol absorption by neomycin.

Kesäniemi, Y. A.; Grundy, Scott M.

doi:10.1161/01.atv.4.1.41

Cited by 55 publications

(20 citation statements)

References 43 publications

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“…Hypolipidaemic therapy with cholesterol malabsorption by ketoconazole [22], neomycin [45] or sitostanol ester in the present study decreases TR, less so fractional catabolism for LDL apo B. The main reduction of LDL cholesterol, apo B and TR occurred in the dense LDL fraction with no compositional change, while the very dense fraction became apo B enriched.…”

Section: Discussionmentioning

confidence: 47%

Serum cholesterol and cholesterol and lipoprotein metabolism in hypercholesterolaemic NIDDM patients before and during sitostanol ester-margarine treatment

Gylling

Miettinen

1994

Diabetologia

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Summary Cholesterol absorption and metabolism and LDL and HDL kinetics were investigated in 11 hypercholesterolaemic non-insulin-dependent diabetic men off and on a hypolipidaemic treatment with sitostanol ester, (3 g sitostanol daily) dissolved in rapeseed oil margarine, by a double-blind crossover study design. Serum total, VLDL and LDL cholesterol and apoprotein B fell significantly by 6 + 2,12 + 6, 9 + 3 and 6 + 2 %, mean + SEM, and HDL cholesterol was increased by 11 + 4 % (p < 0.05) by sitostanol ester. LDL cholesterol and apoprotein B were significantly decreased in the dense (1.037-1.055 g/ml), but not light, LDL subfraction due to a significantly diminished transport rate for LDL apoprotein B, while the fractional catabolic rate was unchanged. HDL kinetics, measured with autologous apoprotein A I, was unaffected by sitostanol ester. Cholesterol absorption efficiency was markedly reduced from 25 + 2 to 9 + 2 % (p < 0.001) during sitostanol ester followed by proportionately decreased serum plant sterol proportions. Cholesterol precursor sterol proportions in serum, fecal neutral sterol excretion, and cholesterol synthesis, cholesterol transport, and biliary secretion were all significantly increased by sitostanol ester. We conclude that the sitostanol ester-induced decrease in cholesterol absorption compensatorily stimulated cholesterol synthesis, had no effect on fractional catabolic rate, but decreased transport rate for LDL apoprotein B so that serum total, VLDL and LDL cholesterol levels were decreased. Dietary rapeseed oil margarine rich in sitostanol ester was well tolerated, appears to be safe from the nutritional point of view and effective for lowering VLDL and LDL cholesterol and increasing HDL cholesterol in hypercholesterolaemic non-insulin-dependent diabetic subjects. [Diabetologia (1994) 37: 773-780]

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Section: Discussionmentioning

confidence: 47%

Serum cholesterol and cholesterol and lipoprotein metabolism in hypercholesterolaemic NIDDM patients before and during sitostanol ester-margarine treatment

Gylling

Miettinen

1994

Diabetologia

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“…Previous human studies have found a positive association between increased LDL PR and increased cholesterol absorption. 20,21 It is possible, therefore, that increased LDL PR as a result of alcohol in the rabbit might be caused by increased cholesterol absorption. However, our work does not distinguish between this possibility and a direct effect of alcohol on lipoprotein metabolism.…”

Section: Discussionmentioning

confidence: 99%

Effects of Alcohol and Cholesterol Feeding on Lipoprotein Metabolism and Cholesterol Absorption in Rabbits

Latour

Patterson

Kitchens

et al. 1999

ATVB

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Abstract-Alcohol fed to rabbits in a liquid formula at 30% of calories increased plasma cholesterol by 36% in the absence of dietary cholesterol and by 40% in the presence of a 0.5% cholesterol diet. The increase was caused almost entirely by VLDL, IDL, and LDL. Cholesterol feeding decreased the fractional catabolic rate for VLDL and LDL apoprotein by 80% and 57%, respectively, and increased the production rate of VLDL and LDL apoprotein by 75% and 15%, respectively. Alcohol feeding had no effect on VLDL apoprotein production but increased LDL production rate by 55%. he effects of alcohol on cholesterol and lipoprotein metabolism have substantial public health implications. It is generally believed that moderate alcohol consumption reduces coronary heart disease risk because observational studies show that it is associated with elevated HDL cholesterol levels and decreased cardiovascular events. 1-3 However, alcohol has many biological actions, and adverse effects on lipid metabolism and cardiovascular disease risk are also well-known, especially in individuals with familial predisposition to hyperlipidemia. 4,5 Thus, the results of alcohol consumption are likely to reflect a balance that might be positive or negative in a given individual. Clearly, a more complete understanding of the interaction between alcohol and lipid metabolism is needed.To investigate the effects of alcohol under controlled dietary conditions, we previously reported the application of cholesterol-and alcohol-containing liquid formula diets that are palatable and allow good weight gain and gastrointestinal function in rabbits. 6,7 This work showed that instead of protecting against atherosclerosis, ethanol feeding at 20% to 30% of calories in the presence of dietary cholesterol (0.5% by weight) increased both plasma lipoproteins and aortic atherosclerotic lesions. In the presence of dietary cholesterol, plasma VLDL and LDL doubled when alcohol was substituted for carbohydrates at 30% of calories, and aortic arch cholesterol content increased fourfold. The current work was performed to investigate potential mechanism(s) responsible for these adverse alcohol-induced changes. The kinetics of VLDL and LDL were determined by tracer methods after varying periods of dietary treatment, and cholesterol absorption was measured at the end of the experiment. The results suggest that alcohol induced increased cholesterol absorption. As a result fractional catabolic rates for VLDL and LDL decreased and production of LDL increased. These changes probably account for the adverse effects of alcohol on lipoprotein metabolism and atherosclerosis in the cholesterol-fed rabbit. Methods Animals and DietForty female New Zealand White rabbits were housed individually during a 6-week study. The animals were divided into 4 groups at the beginning of the trial and fed liquid diets as previously described in detail. 7 All diets were isonitrogenous and isocaloric with alcohol replacing carbohydrate. The control diet (L) contained 18% fat and 56% carbohydrate and was f...

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“…Probucol and neomycin are each known to reduce both LDL and HDL,28 29 but the decrease in HDL cholesterol was not seen in patients taking cholestyramine alone. The major effect of lipid lowering treatment overall was to decrease LDL cholesterol by 18%, which resulted in a significant increase in the HDL ratio.…”

Section: Discussionmentioning

confidence: 99%

Coronary artery disease and haemostatic variables in heterozygous familial hypercholesterolaemia.

Sugrue¹,

Trayner²,

Thompson³

et al. 1985

Heart

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SUMMARY Haemostatic variables were measured in 61 patients with heterozygous familial hypercholesterolaemia, 32 of whom had evidence of coronary heart disease. Age adjusted mean concentrations of plasma fibrinogen and factor VIII were significantly higher in these patients than in the 29 patients without coronary heart disease, but there were no significant differences in serum lipid concentrations between the two groups. Comparisons in 30 patients taking and not taking lipid lowering drugs showed lower values for low density lipoprotein cholesterol, high density lipoprotein cholesterol and antithrombin III, and a higher high density lipoprotein ratio while receiving treatment. The results suggest that hypercoagulability may play a role in the pathogenesis of coronary heart disease in patients with familial hypercholesterolaemia.Premature coronary disease is a characteristic feature of heterozygous familial hypercholesterolaemia and up to 50% of male and 25% of female patients with familial hypercholesterolaemia develop symptoms of coronary ischaemia by the age of 50. 1 2 Increased concentrations of low density lipoprotein (LDL) play a major role in the pathogenesis of this premature atherosclerosis, but accelerated intravascular coagulation3 and increased plasma fibrinogen concentrations have also been reported.4 5 Preliminary results from the Northwick Park heart study have shown an association between high plasma concentrations of factor VII, factor VIII, and fibrinogen and an increased risk of subsequent cardiovascular death.6 We have therefore measured these and other haemostatic variables in patients with familial hypercholesterolaemia with or without overt coronary heart disease and in addition have studied the effects of hypolipidaemic drugs on these variables.

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Turnover of low density lipoproteins during inhibition of cholesterol absorption by neomycin.

Cited by 55 publications

References 43 publications

Serum cholesterol and cholesterol and lipoprotein metabolism in hypercholesterolaemic NIDDM patients before and during sitostanol ester-margarine treatment

Serum cholesterol and cholesterol and lipoprotein metabolism in hypercholesterolaemic NIDDM patients before and during sitostanol ester-margarine treatment

Effects of Alcohol and Cholesterol Feeding on Lipoprotein Metabolism and Cholesterol Absorption in Rabbits

Coronary artery disease and haemostatic variables in heterozygous familial hypercholesterolaemia.

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