Regulation of Lipid and Lipoprotein Metabolism by PPAR Activators
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Philippe Gervois
Abstract
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.
Copyright © 2000 by Walter de Gruyter GmbH & Co. KG
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Articles in the same Issue
- The Millenium 2000; Laboratory Medicine – from Where? to Where?
- Regulation of Lipid and Lipoprotein Metabolism by PPAR Activators
- Laboratory Screening for Erythropoietin Abuse in Sport: an Emerging Challenge
- Antioxidant Enzyme Activities and Total Nitrite/ Nitrate Levels in the Collar Model. Effect of Nicardipine
- Enzyme Immunoassays for Fragments (Epitopes) of Human Proatrial Natriuretic Peptides
- Transient Nature of Interference Effects from Heterophile Antibodies: Examples of Interference with Cardiac Marker Measurements
- Comparison of Procalcitonin, sCD14 and Interleukin-6 Values in Septic Patients
- Changes in Bone Turnover and Deoxypyridinoline Levels in Epileptic Patients
- Analytical Performance of the Fully Automated AxSYM(r) Estradiol Assay
- Impacts of Laboratory Methodology on Medical Thinking in the 19th Century
- Reference Intervals for Erythropoietin Measurement by the JCL EIA Assay Need to Be Determined Locally
- The Physical Basis of Biochemistry. By Peter R. Bergethon
- European Science. Science funding: the European dimension. A discussion meeting held at the Royal Society, Tuesday 17 March, 1998
- IFCC News
