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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

IMPACT FACTOR increased in 2015: 3.017
Rank 5 out of 30 in category Medical Laboratory Technology in the 2014 Thomson Reuters Journal Citation Report/Science Edition

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Source Normalized Impact per Paper (SNIP) 2015: 0.982
Impact per Publication (IPP) 2015: 2.238

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Regulation of Lipid and Lipoprotein Metabolism by PPAR Activators

Philippe Gervois / Inés Pineda Torra / Jean-Charles Fruchart / Bart Staels

Citation Information: Clinical Chemistry and Laboratory Medicine. Volume 38, Issue 1, Pages 3–11, ISSN (Print) 1434-6621, DOI: 10.1515/CCLM.2000.002, June 2005

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The peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. PPARα, the first identified PPAR family member, is principally expressed in tissues exhibiting high rates of β-oxidation such as liver, kidney, heart and muscle. PPARγ, on the other hand, is expressed at high levels in adipose tissue. PPARs are activated by dietary fatty acids and eicosanoids, as well as by pharmacological drugs, such as fibrates for PPARα and glitazones for PPARγ. PPARα mediates the hypolipidemic action of fibrates in the treatment of hypertriglyceridemia and hypoalphalipoproteinemia. PPARα is considered a major regulator of intra- and extracellular lipid metabolism. Upon fibrate activation, PPARα down-regulates hepatic apolipoprotein C-III and increases lipoprotein lipase gene expression, key players in triglyceride metabolism. In addition, PPARα activation increases plasma HDL cholesterol via the induction of hepatic apolipoprotein A-I and apolipoprotein A-II expression in humans. Glitazones exert a hypotriglyceridemic action via PPARγ-mediated induction of lipoprotein lipase expression in adipose tissue. PPARs play also a role in intracellular lipid metabolism by up-regulating the expression of enzymes involved in conversion of fatty acids in acyl-coenzyme A esters, fatty acid entry into mitochondria and peroxisomal and mitochondrial fatty acid catabolism. These observations have provided the molecular basis leading to a better understanding of the mechanism of action of fibrates and glitazones on lipid and lipoprotein metabolism and identify PPARs as attractive targets for the rational design of more potent lipid-lowering drugs.

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