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: 13.22). 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
    • "fatty-acid (FA) oxidation, which provides energy for peripheral tissues [Lefebvre et al. 2006]. The involvement in antioxidant pathways is suggested to contribute to the pathogenesis of age-related macular degeneration (AMD) [Del V Cano and Gehlbach 2007; Lefebvre et al. 2006]. PPARb is expressed predominantly in the gut, kidney, and heart; and is involved in lipid metabolism, cell survival, wound healing, embryonic implantation, and development of the central nervous system [Berger et al. 2005]. "
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    ABSTRACT: Abstract Peroxisome proliferator-activated receptor-gamma (PPAR-γ) belongs to the nuclear hormone receptor superfamily. Apart from being involved in lipid metabolism, like its other subtypes PPAR α and β, it is implicated to be crucial for successful placentation. While its role in extravillous trophoblast (EVT) differentiation has been studied, the involvement in villous trophoblast (VT) differentiation, fatty-acid metabolism, inflammatory responses, and oxidative pathways during pregnancy deserves more attention. PPAR-γ's potential role in balancing structural development and functional responsibilities at the maternal-fetal interface suggest a more central role for the receptor. The central role of PPAR-γ in pathways related to placental pathologies suggests a potential role of PPAR-γ in placental function. The molecular regulation of PPAR-γ in this context has been widely disregarded. In this review, we discuss the less explored functions of PPAR-γ in the areas of immunological responses and management of oxidative stress in the placenta. We also shed light on the involvement of PPAR-γ in pathologic pregnancies and briefly discuss the current models in the field. The ability to modulate PPAR-γ's activity using already available drugs makes it a tempting therapeutic target. Elucidation of the molecular pathways and specific targets regulated by PPAR-γ will provide more information on the role of PPAR-γ in placentation and related disorders in pregnancy. Furthermore it will close the critical gap in our knowledge about the differential regulation of PPAR-γ in the two trophoblast lineages. This will help to evaluate the usefulness and timing of PPAR-γ modulation in at risk pregnancies to improve placental and endothelial function.
    No preview · Article · Dec 2014 · Systems Biology in Reproductive Medicine
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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). "

    Full-text · Dataset · Nov 2014
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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). "

    Full-text · Dataset · Nov 2014
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