Pharmacological LXR activation reduces presence of SR-B1 in liver membranes contributing to LXR-mediated induction of HDL-cholesterol

In order to study the mechanism by which increasing unsaturation of dietary fat lowers HDL-cholesterol levels, we studied various measures of HDL metabolism in hamsters fed with fats with different degrees of saturation. Hamsters were fed on a cholesterol-enriched (1 g/kg) semipurified diet containing 200 g/kg of maize oil, olive oil, or palm oil for 9 weeks. Increasing saturation of dietary fat resulted in increasing concentrations of total plasma cholesterol (4·29 (SD 0·51), 5·30 (sd 0·67) and 5·58 (sd 0·76) mmol/l respectively,n12) and HDL-cholesterol (3·31 (sd 0·50), 3·91 (sd 0·12) and 3·97 (sd 0·43) mmol/l) and these concentrations were significantly higher (P< 0·05) in the palm-oil and olive-oil-fed hamsters compared with the maize-oil group. Total plasma triacylglycerol levels also increased with increasing fat saturation (1·01 (sd 0·59), 1·56 (sd 0·65) and 2·75 (sd 1·03) mmol/l) and were significantly higher (P< 0·05) in the palm-oil group compared with the olive-oil and maize-oil-fed hamsters. The three diets did not have differential effects on plasma activity levels of lecithin: cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP). Levels of phospholipid transfer protein (PLTP) tended to be higher with increasing fat saturation but this effect was not significant. The capacity of liver membranes to bind human HDL3was significantly higher (P< 0·05) in the hamsters fed with maize oil (810 (sd 100) ng HDL3protein/mg membrane protein,n4) compared with those fed on palm oil (655 (sd 56) ng/mg), whereas the olive-oil group had intermediate values (674 (sd 26) ng/mg). The affinity of HDL3for the binding sites was not affected by the type of dietary fat. Hepatic lipase (EC3.1.1.3) activity, measured in liver homogenates, increased with increasing fat saturation. We conclude that dietary maize oil, when compared with either olive oil or palm oil, may lower HDL-cholesterol concentrations by enhancing HDL binding to liver membranes.

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Decreasing dietary fat saturation lowers HDL-cholesterol and increases hepatic HDL binding in hamsters

British Journal Of Nutrition ◽

10.1017/s0007114500000192 ◽

2000 ◽

Vol 83 (2) ◽

pp. 151-159 ◽

Cited By ~ 14

Author(s):

A. H. M. Terpstra ◽

P. van den Berg ◽

H. Jansen ◽

A. C. Beynen ◽

A. van Tol

Keyword(s):

Olive Oil ◽

Palm Oil ◽

Dietary Fat ◽

Hepatic Lipase ◽

Hdl Cholesterol ◽

Total Plasma ◽

Fat Saturation ◽

Transfer Protein ◽

Liver Membranes ◽

Maize Oil

In order to study the mechanism by which increasing unsaturation of dietary fat lowers HDL-cholesterol levels, we studied various measures of HDL metabolism in hamsters fed with fats with different degrees of saturation. Hamsters were fed on a cholesterol-enriched (1 g/kg) semipurified diet containing 200 g/kg of maize oil, olive oil, or palm oil for 9 weeks. Increasing saturation of dietary fat resulted in increasing concentrations of total plasma cholesterol (4·29 (SD 0·51), 5·30 (sd 0·67) and 5·58 (sd 0·76) mmol/l respectively,n12) and HDL-cholesterol (3·31 (sd 0·50), 3·91 (sd 0·12) and 3·97 (sd 0·43) mmol/l) and these concentrations were significantly higher (P< 0·05) in the palm-oil and olive-oil-fed hamsters compared with the maize-oil group. Total plasma triacylglycerol levels also increased with increasing fat saturation (1·01 (sd 0·59), 1·56 (sd 0·65) and 2·75 (sd 1·03) mmol/l) and were significantly higher (P< 0·05) in the palm-oil group compared with the olive-oil and maize-oil-fed hamsters. The three diets did not have differential effects on plasma activity levels of lecithin: cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP). Levels of phospholipid transfer protein (PLTP) tended to be higher with increasing fat saturation but this effect was not significant. The capacity of liver membranes to bind human HDL3was significantly higher (P< 0·05) in the hamsters fed with maize oil (810 (sd 100) ng HDL3protein/mg membrane protein,n4) compared with those fed on palm oil (655 (sd 56) ng/mg), whereas the olive-oil group had intermediate values (674 (sd 26) ng/mg). The affinity of HDL3for the binding sites was not affected by the type of dietary fat. Hepatic lipase (EC3.1.1.3) activity, measured in liver homogenates, increased with increasing fat saturation. We conclude that dietary maize oil, when compared with either olive oil or palm oil, may lower HDL-cholesterol concentrations by enhancing HDL binding to liver membranes.

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Uptake of apolipoprotein E-rich and apolipoprotein E-poor subfractions of high-density lipoprotein by liver membranes and HepG2 cells

Biochemical Journal ◽

10.1042/bj3110611 ◽

1995 ◽

Vol 311 (2) ◽

pp. 611-615 ◽

Cited By ~ 1

Author(s):

Y D Fragoso ◽

E R Skinner

Keyword(s):

High Density Lipoprotein ◽

Apolipoprotein E ◽

Hepg2 Cells ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

High Density ◽

Selective Uptake ◽

Hdl Subfractions ◽

Apo E ◽

Liver Membranes

Apolipoprotein (apo) E plays an important role in mediating high-density lipoprotein (HDL) cholesterol transport and uptake by the liver. Evidence for and against the existence of conventional liver receptors for HDL containing apoE have been reported, although the selective uptake of the cholesterol moiety of HDL has been demonstrated. The present study investigated the hepatic uptake of subfractions of HDL separated on the basis of their apoE content. Rabbit HDL and its apoE-rich and apoE-poor subfractions, separated by heparin-Sepharose affinity chromatography, were labelled in their apoprotein moieties with [14C]sucrose and in their cholesteryl ester moiety with 3H. No binding of either subfraction to rabbit liver membranes could be detected. With cultured HepG2 cells, however, there was a high uptake of 3H but a very low uptake of 14C from both HDL subfractions, demonstrating that selective uptake was operating. Addition of unlabelled apoE-poor HDL inhibited the uptake of both labels from the two subfractions to the same extent. These studies, which differed from previously reported investigations by employing native homologous HDL subfractions of known apolipoprotein composition, demonstrated that apoE is not directly involved in the selective uptake of HDL cholesterol by the liver. In the absence of specific binding sites on liver membranes, it is suggested that an alternative mechanism might exist for the clearance of HDL cholesterol from the plasma.

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W14.362 Sex-specific effect of APOAV variant VAL153S met on plasma levels of HDL-cholesterol

Atherosclerosis ◽

10.1016/s0021-9150(04)90361-9 ◽

2004 ◽

Vol 5 (1) ◽

pp. 84

Author(s):

J HUBACEK

Keyword(s):

Plasma Levels ◽

Specific Effect ◽

Hdl Cholesterol

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Once a rising star of CV prevention, boosting HDL cholesterol falls to earth

Internal Medicine News ◽

10.1016/s1097-8690(13)70046-5 ◽

2013 ◽

Vol 46 (2) ◽

pp. 1-33 ◽

Cited By ~ 1

Author(s):

BRUCE JANCIN

Keyword(s):

Hdl Cholesterol

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Effects of the Tibetan herbal preparation PADMA 28 on blood lipids and lipid oxidisability in subjects with mild hypercholesterolaemia

VASA ◽

10.1024/0301-1526.34.1.11 ◽

2005 ◽

Vol 34 (1) ◽

pp. 11-17 ◽

Cited By ~ 12

Author(s):

Brunner-La Rocca ◽

Schindler ◽

Schlumpf ◽

Saller ◽

Suter

Keyword(s):

Endothelial Dysfunction ◽

Blood Lipids ◽

Ex Vivo ◽

Hdl Cholesterol ◽

Blood Lipid ◽

Tibetan Medicine ◽

Double Blind ◽

Intraarterial Infusion ◽

Padma 28

Background: Previous studies showed an anti-atherosclerotic effect of PADMA 28, an herbal formula based on Tibetan medicine. As the mechanisms of action are not fully understood, we investigated whether PADMA 28 may lower blood lipids and lipid oxidisability, and affect early endothelial dysfunction. Patients and methods: Sixty otherwise healthy subjects with total cholesterol ≥5.2 mmol/l and < 8.0 mmol/l were randomly assigned to placebo or PADMA 28, 3 x 2 capsules daily, for 4 weeks (double-blind). Blood lipids (total, LDL-, and HDL-cholesterol, triglycerides, Apo-lipoprotein A1 and B) and ex vivo lipid oxidisability were measured before and after treatment. In a subset of 24 subjects, endothelial function was assessed using venous occlusion plethysmography with intraarterial infusion of acetylcholine. Isolated LDL and plasma both untreated and pre-treated with PADMA 28 extract were oxidised by the radical generator AAPH. Conjugated diene formation was measured at 245 nm. Results: Blood lipids did not change during the study in both groups. In contrast to previous reports in mild hypercholesterolaemia, no endothelial dysfunction was seen and, consequently, was not influenced by therapy. Ex vivo blood lipid oxidisability was significantly reduced with PADMA 28 (area under curve: 5.29 ± 1.62 to 4.99 ± 1.46, p = 0.01), and remained unchanged in the placebo group (5.33 ± 1.88 to 5.18 ± 1.78, p > 0.1). This effect persisted one week after cessation of medication. In vitro experiments confirmed the prevention of lipid peroxidation in the presence of PADMA 28 extracts. Persistent protection was also seen for LDL isolated from PADMA 28-pretreated blood after being subjected to rigorous purification. Conclusions: This study suggests that the inhibition of blood lipid oxidisability by PADMA 28 may play a role in its anti-atherosclerotic effect.

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The Effect of n-3 Fatty Acids on Lipids and Haemostasis in Patients with Type lla and Type IV Hyperlipidaemia

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646906 ◽

1989 ◽

Vol 62 (02) ◽

pp. 797-801 ◽

Cited By ~ 24

Author(s):

E Berg Schmidt ◽

E Ernst ◽

K Varming ◽

J O Pedersen ◽

J Dyerberg

Keyword(s):

Fatty Acids ◽

Plasma Lipids ◽

Plasma Cholesterol ◽

Hdl Cholesterol ◽

Apolipoprotein A1 ◽

Type Iv ◽

Before And After ◽

Von Willebrand ◽

Willebrand Factor ◽

Factor Antigen

SummaryPlasma lipids and haemostasis were investigated in 17 patients with hyperlipidaemia before and after 6 weeks supplementation with 6 g n-3 fatty acids. Nine of the patients had type IIa and 8 had type IV hyperlipidaemia. No effect on plasma cholesterol, LDL- or HDL-cholesterol were seen, but plasma triglycerides decreased after n-3 supplementation. Apolipoprotein B increased and apolipoprotein A1 decreased after the oil supplement. The bleeding time was prolonged, but platelet aggregation was unaltered by n-3 fatty acids. Protein C activity increased in type II a and decreased in type IV after the supplement. Fibrinolysis was markedly depressed while von Willebrand factor antigen was reduced after intake of n-3 fatty acids.

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Platelet Aggregation and Plasma Lipoproteins in Alcoholics During Alcohol Withdrawal

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661516 ◽

1986 ◽

Vol 55 (02) ◽

pp. 173-177 ◽

Cited By ~ 18

Author(s):

K Desai ◽

J S Owen ◽

D T Wilson ◽

R A Hutton

Keyword(s):

Platelet Aggregation ◽

Alcohol Withdrawal ◽

Ldl Cholesterol ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Plasma Lipoprotein ◽

Cholesterol Concentration ◽

Arachidonic Acid Content ◽

Low Density

SummaryPlatelet aggregation, platelet lipid composition and plasma lipoprotein concentrations were measured each week in a group of seventeen alcoholics, without overt liver disease, for one month, following acute, total alcohol withdrawal. The platelets were initially hypoaggregable but, within 1-2 weeks of cessation of drinking, they became hyperaggregable and then gradually returned towards normal values. Hyperaggregability could not be explained by increases in either the cholesterol or the arachidonic acid content of the platelets. Plasma very-low-density lipoprotein cholesterol levels remained high throughout the study, but the initially raised levels of high-density lipoprotein (HDL) cholesterol fell by 26%. Low-density lipoprotein (LDL) cholesterol concentration rose by 10% after two weeks of withdrawal but then returned to about the starting level. The resulting changes in the plasma LDL-cholesterol: HDL-cholesterol ratio, which had increased by more than 50% after two weeks of abstinence, essentially paralleled the time course of enhanced platelet reactivity in all but four of the alcoholics. These findings suggest that alterations in plasma lipoprotein concentrations during acute alcohol withdrawal may be a contributory factor to the haemostatic disorders present in such patients.

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