The transcriptional coactivator peroxisome proliferator activated receptor (PPAR)gamma coactivator-1 alpha and the nuclear receptor PPAR alpha control the expression of glycerol kinase and metabolism genes independently of PPAR gamma activation in human white adipocytes.
2007
Mazzucotelli, Anne | Viguerie, Nathalie | Tiraby, Claire | Annicotte, Jean-Sébastien | Mairal, Aline | Klimcáková, Eva | Lepin, Emmanuelle | Delmar, Paul | Dejean, Sébastien | Tavernier, Geneviève | Lefort, Corinne | Hidalgo, Juan | Pineau, Thierry | Fajas, Lluis | Clément, Karine | Langin, Dominique | Laboratoire de Biochimie [CHU Toulouse] ; Institut Fédératif de Biologie (IFB) ; Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse] ; Centre Hospitalier Universitaire de Toulouse (CHU Toulouse) | Institut de médecine moléculaire de Rangueil (I2MR) ; Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM) | Franco-Czech Laboratory for Clinical Research on Obesity ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Univerzita Karlova [Praha, Česká republika] = Charles University [Prague, Czech Republic] (UK) | Métabolisme et cancer ; Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM) | Mathématiques Appliquées aux Systèmes - EA 4037 (MAS) ; Ecole Centrale Paris | Laboratoire de Statistique et Probabilités (LSP) ; Institut National des Sciences Appliquées - Toulouse (INSA Toulouse) ; Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS) | Institute of Neurosciences ; Universitat de Barcelona (UB) | Pharmacology and Toxicology Laboratory ; Institut National de la Recherche Agronomique (INRA) | Centre de Recherche des Cordeliers (CRC (UMR_S 872)) ; Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
International audience
Mostrar más [+] Menos [-]Inglés. OBJECTIVE: The purpose of this work was to determine the pattern of genes regulated by peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1 alpha (PGC-1 alpha) in human adipocytes and the involvement of PPARalpha and PPARgamma in PGC-1 alpha transcriptional action. RESEARCH DESIGN AND METHODS: Primary cultures of human adipocytes were transduced with a PGC-1 alpha adenovirus and treated with PPARgamma and PPARalpha agonists. Variation in gene expression was assessed using pangenomic microarrays and quantitative RT-PCR. To investigate glycerol kinase (GyK), a target of PGC-1 alpha, we measured enzymatic activity and glycerol incorporation into triglycerides. In vivo studies were performed on wild-type and PPARalpha(-/-) mice. The GyK promoter was studied using chromatin immunoprecipitation and promoter reporter gene assays. RESULTS: Among the large number of genes regulated by PGC-1 alpha independently of PPARgamma, new targets involved in metabolism included the gene encoding GyK. The induction of GyK by PGC-1 alpha was observed at the levels of mRNA, enzymatic activity, and glycerol incorporation into triglycerides. PPARalpha was also upregulated by PGC-1 alpha. Its activation led to an increase in GyK expression and activity. PPARalpha was shown to bind and activate the GyK promoter. Experiments in mice confirmed the role of PGC-1 alpha and PPARalpha in the regulation of GyK in vivo. CONCLUSIONS: This work uncovers novel pathways regulated by PGC-1 alpha and reveals that PPARalpha controls gene expression in human white adipocytes. The induction of GyK by PGC-1 alpha and PPARalpha may promote a futile cycle of triglyceride hydrolysis and fatty acid reesterification.
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