Peroxisome Proliferator Activated Receptors and Lipoprotein Metabolism

Plasma lipoproteins are responsible for carrying triglycerides and cholesterol in the blood and ensuring their delivery to target organs. Regulation of lipoprotein metabolism takes place at numerous levels including via changes in gene transcription. An important group of transcription factors that...

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Main Author: Sander Kersten
Format: Article
Language:English
Published: Wiley 2008-01-01
Series:PPAR Research
Online Access:http://dx.doi.org/10.1155/2008/132960
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author Sander Kersten
author_facet Sander Kersten
author_sort Sander Kersten
collection DOAJ
description Plasma lipoproteins are responsible for carrying triglycerides and cholesterol in the blood and ensuring their delivery to target organs. Regulation of lipoprotein metabolism takes place at numerous levels including via changes in gene transcription. An important group of transcription factors that mediates the effect of dietary fatty acids and certain drugs on plasma lipoproteins are the peroxisome proliferator activated receptors (PPARs). Three PPAR isotypes can be distinguished, all of which have a major role in regulating lipoprotein metabolism. PPARα is the molecular target for the fibrate class of drugs. Activation of PPARα in mice and humans markedly reduces hepatic triglyceride production and promotes plasma triglyceride clearance, leading to a clinically significant reduction in plasma triglyceride levels. In addition, plasma high-density lipoprotein (HDL)-cholesterol levels are increased upon PPARα activation in humans. PPARγ is the molecular target for the thiazolidinedione class of drugs. Activation of PPARγ in mice and human is generally associated with a modest increase in plasma HDL-cholesterol and a decrease in plasma triglycerides. The latter effect is caused by an increase in lipoprotein lipase-dependent plasma triglyceride clearance. Analogous to PPARα, activation of PPARβ/δ leads to increased plasma HDL-cholesterol and decreased plasma triglyceride levels. In this paper, a fresh perspective on the relation between PPARs and lipoprotein metabolism is presented. The emphasis is on the physiological role of PPARs and the mechanisms underlying the effect of synthetic PPAR agonists on plasma lipoprotein levels.
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spelling doaj-art-9c60421e0f034792b0e37431d4b1ed292025-02-03T01:12:36ZengWileyPPAR Research1687-47571687-47652008-01-01200810.1155/2008/132960132960Peroxisome Proliferator Activated Receptors and Lipoprotein MetabolismSander Kersten0Nutrigenomics Consortium and Nutrition, Metabolism and Genomics Group, Wageningen University, P.O. Box 8129, Wageningen, EV 6700, The NetherlandsPlasma lipoproteins are responsible for carrying triglycerides and cholesterol in the blood and ensuring their delivery to target organs. Regulation of lipoprotein metabolism takes place at numerous levels including via changes in gene transcription. An important group of transcription factors that mediates the effect of dietary fatty acids and certain drugs on plasma lipoproteins are the peroxisome proliferator activated receptors (PPARs). Three PPAR isotypes can be distinguished, all of which have a major role in regulating lipoprotein metabolism. PPARα is the molecular target for the fibrate class of drugs. Activation of PPARα in mice and humans markedly reduces hepatic triglyceride production and promotes plasma triglyceride clearance, leading to a clinically significant reduction in plasma triglyceride levels. In addition, plasma high-density lipoprotein (HDL)-cholesterol levels are increased upon PPARα activation in humans. PPARγ is the molecular target for the thiazolidinedione class of drugs. Activation of PPARγ in mice and human is generally associated with a modest increase in plasma HDL-cholesterol and a decrease in plasma triglycerides. The latter effect is caused by an increase in lipoprotein lipase-dependent plasma triglyceride clearance. Analogous to PPARα, activation of PPARβ/δ leads to increased plasma HDL-cholesterol and decreased plasma triglyceride levels. In this paper, a fresh perspective on the relation between PPARs and lipoprotein metabolism is presented. The emphasis is on the physiological role of PPARs and the mechanisms underlying the effect of synthetic PPAR agonists on plasma lipoprotein levels.http://dx.doi.org/10.1155/2008/132960
spellingShingle Sander Kersten
Peroxisome Proliferator Activated Receptors and Lipoprotein Metabolism
PPAR Research
title Peroxisome Proliferator Activated Receptors and Lipoprotein Metabolism
title_full Peroxisome Proliferator Activated Receptors and Lipoprotein Metabolism
title_fullStr Peroxisome Proliferator Activated Receptors and Lipoprotein Metabolism
title_full_unstemmed Peroxisome Proliferator Activated Receptors and Lipoprotein Metabolism
title_short Peroxisome Proliferator Activated Receptors and Lipoprotein Metabolism
title_sort peroxisome proliferator activated receptors and lipoprotein metabolism
url http://dx.doi.org/10.1155/2008/132960
work_keys_str_mv AT sanderkersten peroxisomeproliferatoractivatedreceptorsandlipoproteinmetabolism