Abstract:
:For the last 30 years fibrates have been widely prescribed to treat human dyslipidemia. However, the primary mechanism by which they lower plasma lipid levels is still unknown. Studies with transgenic mice have suggested that changes in apoC-III expression levels have a dramatic influence on plasma triglyceride levels. These results suggested that fibrates could reduce lipid levels by lowering apoC-III gene expression. In the current studies, we sought to determine whether the selected fibrates, bezafibrate, clofibrate, fenofibrate, and gemfibrozil, could reduce hepatic apoC-III mRNA and plasma apoC-III levels. Chow-fed rats were orally gavaged daily with a dosing vehicle alone or with 100 mg/kg of each of the fibrates for 1 week and in addition with gemfibrozil for 2 weeks. Bezafibrate and fenofibrate lowered plasma triglyceride by approximately half and dramatically reduced hepatic apoC-III mRNA and plasma apoC-III levels. In contrast, clofibrate did not reduce plasma triglyceride levels and only partially reduced apoC-III mRNA and plasma protein levels. Gemfibrozil strongly reduced plasma triglyceride levels and had an intermediate but significant effect on apoC-III mRNA and plasma apoC-III levels. Some of the fibrates, especially gemfibrozil also reduced plasma apoC-II levels, an effect that could contribute to the observed triglyceride-lowering effect. In addition, the ratio of plasma apoE to plasma apoC-II plus apoC-III was strongly and inversely correlated with plasma triglyceride levels. As plasma apoE levels were not reduced in gemfibrozil-treated animals, this could also have contributed to the triglyceride-lowering effect of this fibrate. Fibrate-mediated triglyceride lowering was not the result of a decreased apoB or VLDL production and, therefore, suggested an enhanced VLDL remnant catabolism. Our results suggest that the mechanism by which fibrates lower plasma triglycerides is by reducing the level of hepatic apoC-III expression.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Haubenwallner S,Essenburg AD,Barnett BC,Pape ME,DeMattos RB,Krause BR,Minton LL,Auerbach BJ,Newton RS,Leff Tsubject
Has Abstract,Author List Incompletepub_date
1995-12-01 00:00:00pages
2541-51issue
12eissn
0022-2275issn
1539-7262journal_volume
36pub_type
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abstract::Free fat cells and stromal-vascular cells were prepared from rat adipose tissue by incubation with collagenase. NH(4)OH-NH(4)Cl extracts of acetone-ether powders prepared from fat cells contained lipoprotein lipase activity but extracts of stromal-vascular cells did not. Intact fat cells released lipoprotein lipase ac...
journal_title:Journal of lipid research
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journal_title:Journal of lipid research
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abstract::An in vitro method is presented which measures valid, unidirectional uptake rates for lipids across the intestinal brush border. This method combines analysis by a newly devised, double isotope counting system for solubilized tissue with the use of a nonabsorbable marker to correct gross uptake determinations for cont...
journal_title:Journal of lipid research
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abstract::Enzymes associated with glycerolipid biosynthesis were examined in microsomal fractions of liver and adipose tissue obtained from swine of various ages. Generally, liver glycerophosphate acyltransferase, phosphatidate phosphohydrolase, diglyceride acyltransferase, and choline phosphotransferase activities were substan...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1979-02-01 00:00:00
abstract::High density lipophorin (HDLp is the main lipoprotein found in resting insect hemolymph. It has, in general, two molecules of apolipoproteins: apoLp-I (250 kDa) and apoLp-II (80 kDa) and a variable lipid content which ranges from 35% to 59% (w/w). Diacylglycerols (DG), phospholipids (PL), and hydrocarbons (HC) are the...
journal_title:Journal of lipid research
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abstract::Labeled cholesterol esters were incorporated into chylomicrons in vitro by adding an acetone solution of the cholesterol ester to a suspension of washed chylomicrons. The physical and metabolic properties of the added labeled ester were the same as those of cholesterol esters incorporated into chylomicrons in vivo, ex...
journal_title:Journal of lipid research
pub_type: 杂志文章
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1993-05-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1967-09-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1987-03-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1988-07-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M073882
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M500221-JLR200
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abstract::To study the mechanism of alcoholic hypertriglyceridemia, baboons were pair-fed liquid diets containing 50% of energy as ethanol or as additional carbohydrate for 5-16 months. Alcohol-fed animals developed hypertriglyceridemia and early stages of alcoholic injury, namely fatty liver with or without perivenular fibrosi...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1986-10-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1994-12-01 00:00:00
abstract::Apolipoprotein L is a newly recognized component of human plasma lipoproteins. Mainly associated with apoA-I-containing lipoproteins, it is a marker of distinct HDL subpopulations. In an effort to gain inference as to its as yet unknown function, we studied biological determinants of apoL levels in human plasma. The d...
journal_title:Journal of lipid research
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doi:
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
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journal_title:Journal of lipid research
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doi:
更新日期:1987-12-01 00:00:00
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journal_title:Journal of lipid research
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journal_title:Journal of lipid research
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
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abstract::The addition of a trans isomer of arachidonic acid (20:4 delta 14trans) to rat platelet suspensions inhibited the aggregation induced by 7.5 microM of arachidonic acid. This inhibitory effect of 20:4 delta 14trans was significant at concentrations of 7.5-22.5 microM and the range of inhibition was 20% at an inhibitor/...
journal_title:Journal of lipid research
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doi:
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1983-07-01 00:00:00
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