| The effect of PPAR-alpha agonism on apolipoprotein metabolism in humans. | |
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MedLine Citation:
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PMID: 20005515 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Metabolic syndrome, diabetes and obesity are frequently associated with hypertriglyceridemia, hypercholesterolemia and low HDL levels, a phenotype known as atherogenic dyslipidemia. Atherogenic dyslipidemia and hypertriglyceridemia are frequently treated with fibric acid derivatives which activate the nuclear receptor PPAR-alpha leading to reduce plasma triglycerides and an increase in HDL cholesterol levels. The mechanism by which activation of PPAR-alpha with fibrates improves the plasma lipid profile in patients with atherogenic dyslipidemia and hypertriglyceridemia has been examined in several small studies measuring lipoprotein kinetics. The results of these studies indicate that the changes in lipoprotein metabolism observed in response to fibrate treatment vary according to lipoprotein phenotype. In general, fibrates act to reduce VLDL apoB-100 through enhanced fractional catabolism (clearance) of VLDL apoB-100 with additional effects on reducing VLDL apoB-100 production. LDL apoB-100 levels generally decrease in response to fibrates due to increased LDL fractional catabolism except in those patients with high to very high plasma triglyceride levels (>400mg/dL). Fibrates also increase HDL apoA-I and apoA-II levels by enhancing apoA-I and apoA-II production, although this is partially counteracted by increasing fractional catabolism of these apolipoproteins. The potent and specific PPAR-alpha agonist LY518674, reduced VLDL apoB-100 levels through enhanced fractional catabolism similar to what is seen with fibrates. In contrast to fibrates, LY518674 did not change HDL apoA-I levels in response to due to an increased turnover of apoA-I where an increased fractional catabolic rate entirely counteracted the increase in apoA-I production. The changes in apoB metabolism in response to PPAR-alpha activation with fibrates and specific PPAR-alpha agonists would be expected to reduce the risk of cardiovascular disease. However, the benefit of the enhanced turnover of HDL apoA-I in response to PPAR-alpha activation remains to be determined. |
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Authors:
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Ashish Shah; Daniel J Rader; John S Millar |
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Publication Detail:
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Type: Journal Article; Review Date: 2009-12-14 |
Journal Detail:
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Title: Atherosclerosis Volume: 210 ISSN: 1879-1484 ISO Abbreviation: Atherosclerosis Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-04-30 Completed Date: 2010-08-16 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0242543 Medline TA: Atherosclerosis Country: Ireland |
Other Details:
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Languages: eng Pagination: 35-40 Citation Subset: IM |
Copyright Information:
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Copyright 2009 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
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University of Pennsylvania, Depts. of Medicine and Pharmacology, 652 BRB II/III, 421 Curie Blvd., Philadelphia, PA 19104, United States. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Apolipoproteins
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metabolism* Apolipoproteins A / metabolism Apolipoproteins B / metabolism Humans PPAR alpha / agonists* Propionates / pharmacology* Triazoles / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Apolipoproteins; 0/Apolipoproteins A; 0/Apolipoproteins B; 0/LY 518674; 0/PPAR alpha; 0/Propionates; 0/Triazoles |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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