Article

Sorting out the roles of PPARα in energy metabolism and vascular homeostasis

Département d'Athérosclérose, Institut Pasteur de Lille, INSERM U545, and Université de Lille 2, Lille, France.
Journal of Clinical Investigation (Impact Factor: 13.77). 04/2006; 116(3):571-80. DOI: 10.1172/JCI27989
Source: PubMed

ABSTRACT PPARalpha is a nuclear receptor that regulates liver and skeletal muscle lipid metabolism as well as glucose homeostasis. Acting as a molecular sensor of endogenous fatty acids (FAs) and their derivatives, this ligand-activated transcription factor regulates the expression of genes encoding enzymes and transport proteins controlling lipid homeostasis, thereby stimulating FA oxidation and improving lipoprotein metabolism. PPARalpha also exerts pleiotropic antiinflammatory and antiproliferative effects and prevents the proatherogenic effects of cholesterol accumulation in macrophages by stimulating cholesterol efflux. Cellular and animal models of PPARalpha help explain the clinical actions of fibrates, synthetic PPARalpha agonists used to treat dyslipidemia and reduce cardiovascular disease and its complications in patients with the metabolic syndrome. Although these preclinical studies cannot predict all of the effects of PPARalpha in humans, recent findings have revealed potential adverse effects of PPARalpha action, underlining the need for further study. This Review will focus on the mechanisms of action of PPARalpha in metabolic diseases and their associated vascular pathologies.

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Available from: Giulia Chinetti-Gbaguidi, Jan 15, 2015
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    • "The mechanism of action behind these effects may be related to the ability of individual secoiridoid glucosides isolated from F. excelsior seeds to activate PPARa in vitro; this effect was also observed with the unfractionated extract (Bai et al., 2010). PPARa is a nuclear receptor which has been shown to improve symptoms of the metabolic syndrome (Lefebvre et al., 2006). "
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    • "The mechanism of action behind these effects may be related to the ability of individual secoiridoid glucosides isolated from F. excelsior seeds to activate PPARa in vitro; this effect was also observed with the unfractionated extract (Bai et al., 2010). PPARa is a nuclear receptor which has been shown to improve symptoms of the metabolic syndrome (Lefebvre et al., 2006). "
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    • "Recently, it has become clear that the transcriptional regulation of target genes expression by nuclear receptor is a dynamic process (Hager et al., 2000, 2009, 2004; Stavreva et al., 2012). PPARa plays a key role in the regulation of lipid metabolism and serves as a molecular target for hypolipidemic fibrate drugs (Lefebvre et al., 2006; van Raalte et al., 2004). The activation of PPARa by peroxisome proliferators is a wellcharacterized mode of action of hepatocarcinogenesis in rodents (Corton, 2010; Corton et al., 2014; Peters et al., 2005). "
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