Document Detail


Mechanism of action of fibrates on lipid and lipoprotein metabolism.
MedLine Citation:
PMID:  9808609     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Treatment with fibrates, a widely used class of lipid-modifying agents, results in a substantial decrease in plasma triglycerides and is usually associated with a moderate decrease in LDL cholesterol and an increase in HDL cholesterol concentrations. Recent investigations indicate that the effects of fibrates are mediated, at least in part, through alterations in transcription of genes encoding for proteins that control lipoprotein metabolism. Fibrates activate specific transcription factors belonging to the nuclear hormone receptor superfamily, termed peroxisome proliferator-activated receptors (PPARs). The PPAR-alpha form mediates fibrate action on HDL cholesterol levels via transcriptional induction of synthesis of the major HDL apolipoproteins, apoA-I and apoA-II. Fibrates lower hepatic apoC-III production and increase lipoprotein lipase--mediated lipolysis via PPAR. Fibrates stimulate cellular fatty acid uptake, conversion to acyl-CoA derivatives, and catabolism by the beta-oxidation pathways, which, combined with a reduction in fatty acid and triglyceride synthesis, results in a decrease in VLDL production. In summary, both enhanced catabolism of triglyceride-rich particles and reduced secretion of VLDL underlie the hypotriglyceridemic effect of fibrates, whereas their effect on HDL metabolism is associated with changes in HDL apolipoprotein expression.
Authors:
B Staels; J Dallongeville; J Auwerx; K Schoonjans; E Leitersdorf; J C Fruchart
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Circulation     Volume:  98     ISSN:  0009-7322     ISO Abbreviation:  Circulation     Publication Date:  1998 Nov 
Date Detail:
Created Date:  1998-12-11     Completed Date:  1998-12-11     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2088-93     Citation Subset:  AIM; IM    
Affiliation:
Unité 325 INSERM, Département d'Athérosclérose, Institut Pasteur de Lille, 59019 Lille, France.
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MeSH Terms
Descriptor/Qualifier:
Antilipemic Agents / adverse effects,  pharmacology*,  therapeutic use
Humans
Hyperlipidemias / drug therapy
Lipid Metabolism*
Lipoproteins / metabolism*
Receptors, Cytoplasmic and Nuclear / physiology
Transcription Factors / physiology
Chemical
Reg. No./Substance:
0/Antilipemic Agents; 0/Lipoproteins; 0/Receptors, Cytoplasmic and Nuclear; 0/Transcription Factors

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