scholarly journals Plasma activities of lecithin:cholesterol acyltransferase, lipid transfer proteins and post-heparin lipases in inbred strains of rabbits hypo- or hyper-responsive to dietary cholesterol

1993 ◽  
Vol 293 (3) ◽  
pp. 729-734 ◽  
Author(s):  
G W Meijer ◽  
P N M Demacker ◽  
A Van Tol ◽  
J E M Groener ◽  
J G P Van der Palen ◽  
...  
Keyword(s):  
Plasma Cholesterol ◽  
Strain Difference ◽  
Dietary Cholesterol ◽  
Inbred Strains ◽  
Plasma Lipoproteins ◽  
High Cholesterol Diet ◽  
Lecithin:Cholesterol Acyltransferase ◽  
Triacylglycerol Lipase ◽  
Transfer Protein ◽  
Pltp Activity

Plasma lipoproteins, plasma activities of lecithin:cholesterol acyltransferase (LCAT), phospholipid transfer protein (PLTP), cholesteryl ester transfer protein (CETP) and post-heparin lipases were measured before and after cholesterol challenge in two inbred strains of rabbits with either a high (hyper-responders) or a low (hyporesponders) response of plasma cholesterol to dietary cholesterol. The purpose of this study was to provide clues about the mechanisms underlying the effect of dietary cholesterol on lipoprotein levels and composition, and particularly those underlying the strain difference of this effect. Cholesterol feeding (0.15 g of cholesterol/100 g of diet) caused increased plasma total cholesterol concentrations and an increased ratio of cholesteryl esters:triacylglycerol in all lipoprotein particles in both strains; these effects were significantly greater in hyper- than hypo-responsive rabbits. Feeding on the high-cholesterol diet lowered plasma triacylglycerols in hyper-responders, but caused increased plasma triacylglycerol levels in hyporesponders. This was accompanied by significantly greater increases in the activities of hepatic triacylglycerol lipase and lipoprotein lipase in hyper- than in hypo-responders. Both strains showed a dietary-cholesterol-induced rise in plasma CETP as well as in PLTP activity. The increase in PLTP activity was greater in the hyper-responders, but that of CETP was less. There was no effect of dietary cholesterol on LCAT activity. It is hypothesized that the lipases are involved in the removal of cholesterol-rich lipoproteins.

scholarly journals Selective and independent associations of phospholipid transfer protein and hepatic lipase with the LDL subfraction distribution

2002 ◽  
Vol 43 (8) ◽  
pp. 1256-1263 ◽  
Author(s):  
Susan J. Murdoch ◽  
Molly C. Carr ◽  
Hal Kennedy ◽  
John D. Brunzell ◽  
John J. Albers
Keyword(s):  
Hepatic Lipase ◽  
Premenopausal Women ◽  
Plasma Lipoproteins ◽  
Cholesterol Concentration ◽  
Phospholipid Transfer Protein ◽  
Transfer Protein ◽  
Phospholipid Transfer ◽  
Pltp Activity ◽  
Hdl Metabolism ◽  
Relationship Of

Phospholipid transfer protein (PLTP), hepatic lipase (HL), and lipoprotein lipase (LPL) have all been reported to be intricately involved in HDL metabolism but the effect of PLTP on the apolipoprotein B-containing lipoproteins relative to that of HL and LPL has not been established. Due to our previous observation of a positive correlation of PLTP activity with plasma apoB and LDL cholesterol, the relationship of PLTP with the LDL subfractions was investigated and compared with that of HL and LPL. Plasma lipoproteins from 50 premenopausal women were fractionated by density gradient ultracentrifugation. Correlations were calculated between the cholesterol concentration of each fraction and plasma PLTP, HL, and LPL activity. Plasma PLTP activity was highly, positively, and selectively correlated with the cholesterol concentration of the buoyant LDL/dense IDL fractions, yet demonstrated a complete absence of an association with the dense LDL fractions. In contrast, HL was positively correlated with the dense LDL fractions but showed no association with buoyant LDL. LPL was also positively correlated with several buoyant LDL fractions; however, the correlations were weaker than those of PLTP. PLTP and LPL were positively correlated and HL was negatively correlated with HDL fractions.The results suggest that PLTP and HL may be important and independent determinants of the LDL subpopulation density distributions.

scholarly journals Phosphatidylcholine transfer protein regulates size and hepatic uptake of high-density lipoproteins

2005 ◽  
Vol 289 (6) ◽  
pp. G1067-G1074 ◽  
Author(s):  
Michele K. Wu ◽  
David E. Cohen
Keyword(s):  
Plasma Cholesterol ◽  
High Cholesterol Diet ◽  
Atp Binding ◽  
Cholesterol Diet ◽  
Wild Type ◽  
High Cholesterol ◽  
High Fat ◽  
Transfer Protein ◽  
Phosphatidylcholine Transfer Protein ◽  
Atp Binding Cassette

Phosphatidylcholine transfer protein (PC-TP) is a steroidogenic acute regulatory-related transfer domain protein that is enriched in liver cytosol and binds phosphatidylcholines with high specificity. In tissue culture systems, PC-TP promotes ATP-binding cassette protein A1-mediated efflux of cholesterol and phosphatidylcholine molecules as nascent pre-β-high-density lipoprotein (HDL) particles. Here, we explored a role for PC-TP in HDL metabolism in vivo utilizing 8-wk-old male Pctp−/− and wild-type littermate C57BL/6J mice that were fed for 7 days with either chow or a high-fat/high-cholesterol diet. In chow-fed mice, neither plasma cholesterol concentrations nor the concentrations and compositions of plasma phospholipids were influenced by PC-TP expression. However, in Pctp−/− mice, there was an accumulation of small α-migrating HDL particles. This occurred without changes in hepatic expression of ATP-binding cassette protein A1 or in proteins that regulate the intravascular metabolism and clearance of HDL particles. In Pctp−/− mice fed the high-fat/high-cholesterol diet, HDL particle sizes were normalized, whereas plasma cholesterol and phospholipid concentrations were increased compared with wild-type mice. In the absence of upregulation of hepatic ATP-binding cassette protein A1, reduced HDL uptake from plasma into livers of Pctp−/− mice contributed to higher plasma lipid concentrations. These data indicate that PC-TP is not essential for the enrichment of HDL with phosphatidylcholines but that it does modulate particle size and rates of hepatic clearance.

Cholesteryl Ester Transfer Protein Inhibitors

2016 ◽  
Vol 22 (2) ◽  
pp. 99-104 ◽  
Author(s):  
Julian Hardy McLain ◽  
Andrew Jacob Alsterda ◽  
Rohit R. Arora
Keyword(s):  
Cholesteryl Ester ◽  
Cholesteryl Ester Transfer Protein ◽  
Plasma Cholesterol ◽  
Genetic Research ◽  
Plasma Lipoproteins ◽  
Pharmacologic Therapy ◽  
Atherosclerotic Cardiovascular Disease ◽  
Current Standard ◽  
Transfer Protein ◽  
Cetp Inhibitors

The cholesteryl ester transfer protein (CETP) is a plasma protein that plays an important role in the transfer of lipids between plasma lipoproteins. The CETP inhibitors have been widely studied as a pharmacologic therapy to target plasma cholesterol in order to reduce the risk of atherosclerotic cardiovascular disease . Using CETP inhibitors as cholesterol modifiers was based on the genetic research that found correlations between CETP activity and cholesterol levels. Although CETP inhibitors are successful at altering targeted cholesterol markers, recent phase 3 outcome trials have shown limited benefit on cardiovascular outcomes when combined with the current standard of care. We discuss the science of CETP inhibition, compare the CETP inhibitors developed (torcetrapib, evacetrapib, dalcetrapib, and anacetrapib), the findings from the CETP inhibitor trials, and the future outlook for CETP inhibitors in cholesterol modification.

Effects of dietary flaxseed on vascular contractile function and atherosclerosis during prolonged hypercholesterolemia in rabbits

2006 ◽  
Vol 291 (6) ◽  
pp. H2987-H2996 ◽  
Author(s):  
C. M. C. Dupasquier ◽  
A.-M. Weber ◽  
B. P. Ander ◽  
P. P. Rampersad ◽  
S. Steigerwald ◽  
...  
Keyword(s):  
Vascular Function ◽  
Contractile Function ◽  
Plasma Cholesterol ◽  
Dietary Cholesterol ◽  
Relaxation Response ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Beneficial Effects ◽  
Atherosclerotic Lesions

Dietary flaxseed has significant anti-atherogenic effects. However, the limits of this action and its effects on vascular contractile function are not known. We evaluated the effects of flaxseed supplementation on atherosclerosis and vascular function under prolonged hypercholesterolemic conditions in New Zealand White rabbits assigned to one of four groups for 6, 8, or 16 wk of feeding: regular diet (RG), 10% flaxseed-supplemented diet (FX), 0.5% cholesterol-supplemented diet (CH), and 0.5% cholesterol- and 10% flaxseed-supplemented diet (CF). Cholesterol feeding resulted in elevated plasma cholesterol levels and the development of atherosclerosis. The CF group had significantly less atherosclerotic lesions in the aorta and carotid arteries after 6 and 8 wk than the CH animals. However, the anti-atherogenic effect of flaxseed supplementation was completely attenuated by 16 wk. Maximal tension induced in aortic rings either by KCl or norepinephrine was not impaired by dietary cholesterol until 16 wk. This functional impairment was not prevented by including flaxseed in the high-cholesterol diet. Aortic rings from the cholesterol-fed rabbits exhibited an impaired relaxation response to acetylcholine at all time points examined. Including flaxseed in the high-cholesterol diet completely normalized the relaxation response at 6 and 8 wk and partially restored it at 16 wk. No significant changes in the relaxation response induced by sodium nitroprusside were observed in any of the groups. In summary, dietary flaxseed is a valuable strategy to limit cholesterol-induced atherogenesis as well as abnormalities in endothelial-dependent vasorelaxation. However, these beneficial effects were attenuated during prolonged hypercholesterolemic conditions.

scholarly journals Dietary cholesterol reduces lipoprotein lipase activity in the atherosclerosis-susceptible Bio F1B hamster

2003 ◽  
Vol 89 (3) ◽  
pp. 341-350 ◽  
Author(s):  
Martina A. McAteer ◽  
David C. Grimsditch ◽  
Martin Vidgeon-Hart ◽  
G. Martin Benson ◽  
Andrew M. Salter
Keyword(s):  
Lipoprotein Lipase ◽  
Lipase Activity ◽  
Plasma Cholesterol ◽  
Dietary Cholesterol ◽  
Lipoprotein Metabolism ◽  
Coconut Oil ◽  
Hdl Cholesterol ◽  
High Cholesterol Diet ◽  
Lipoprotein Lipase Activity ◽  
Golden Syrian Hamster

We have compared lipoprotein metabolism in, and susceptibility to atherosclerosis of, two strains of male Golden Syrian hamster, the Bio F1B hybrid and the dominant spot normal inbred (DSNI) strain. When fed a normal low-fat diet containing approximately 40 g fat and 0·3 g cholestero/g, triacylglycerol-rich lipoprotein (chylomicron+VLDL) and HDL-cholesterol were significantly higher (P<0·001) in Bio F1B hamsters than DSNI hamsters. When this diet was supplemented with 150 g coconut oil and either 0·5 or 5·0 g cholestero/g, significant differences were seen in response. In particular, the high-cholesterol diet produced significantly greater increases in plasma cholesterol and triacylglycerol in the Bio F1B compared with the DSNI animals (P=0·002 and P<0·001 for cholesterol and triacylglycerol, respectively). This was particularly dramatic in non-fasting animals, suggesting an accumulation of chylomicrons. In a second experiment, animals were fed 150 g coconut oi/g and 5·0 g cholestero/g for 6 and 12 months. Again, the Bio F1B animals showed dramatic increases in plasma cholesterol and triacylglycerol, and this was confirmed as primarily due to a rise in chylomicron concentration. Post-heparin lipoprotein lipase activity was significantly reduced (P<0·001) in the Bio F1B compared with the DSNI animals at 6 months, and virtually absent at 12 months. Bio F1B animals were also shown to develop significantly more (P<0·001) atherosclerosis. These results indicate that, in the Bio F1B hybrid hamster, cholesterol feeding reduces lipoprotein lipase activity, thereby causing the accumulation of chylomicrons that may be associated with their increased susceptibility to atherosclerosis.

Effect of antecedent diet and of cortisone treatment on cholesterol-4-C14 metabolism in rabbits

1960 ◽  
Vol 198 (2) ◽  
pp. 363-365 ◽  
Author(s):  
Abraham Dury ◽  
Leon Swell
Keyword(s):  
Plasma Cholesterol ◽  
Dietary Cholesterol ◽  
Normal Diet ◽  
High Cholesterol Diet ◽  
High Cholesterol ◽  
Postprandial Period ◽  
Diet Regimen ◽  
Group A ◽  
Metabolic Behavior ◽  
Group B

Metabolic behavior of a test meal containing cholesterol-4-C14 (10 µc C14; 1 gm cholesterol) was observed through 2 days in rabbits previously fed for 35 days a normal diet ( A), and high-cholesterol diet alone ( B) and concurrent cortisone treatment ( C). In the early postprandial period the relative incorporation of cholesterol-4-C14 in the plasma-free and ester cholesterol differed markedly in the three groups. In group C the activity in the plasma cholesterol fractions increased precipitously and maxima specific activities were reached with the 24-hour blood sample while in groups A and B activity in the plasma increased much slower. C14-cholesterol was not incorporated in aorta ester cholesterol of groups A and C 2 days following the labeled cholesterol meal while in aortas of group B a definite amount of ester cholesterol-4-C14 was found. Free and ester cholesterol-C14 quantities in the liver, the plasma and the ileum were greater in group B than that present in respective tissues of group A. On the other hand, larger quantities of liver ester cholesterol-C14 and plasma free cholesterol-C14 were present in group C than in B. The results indicated that metabolic handling of a cholesterol meal was influenced by type of previous diet regimen and that cortisone treatment modified dietary cholesterol behavior in the cholesterol-fed rabbit.

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