PPARγ contributes to PKM2 and HK2 expression in fatty liver

Ganna Panasyuk, Catherine Espeillac, Céline Chauvin, Ludivine A. Pradelli, Yasuo Horie, Akira Suzuki, Jean-Sebastien Annicotte, Lluis Fajas, Marc Foretz, Francisco Verdeguer, Marco Pontoglio, Pascal Ferré, Jean-Yves Scoazec, Morris J. Birnbaum, Jean-Ehrland Ricci and Mario Pende ()
Additional contact information
Ganna Panasyuk: Inserm, U845
Catherine Espeillac: Inserm, U845
Céline Chauvin: Inserm, U845
Ludivine A. Pradelli: Inserm, U895, Centre Méditerranéen de Médecine Moléculaire (C3M), équipe AVENIR
Yasuo Horie: Akita University Graduate School of Medicine
Akira Suzuki: Medical Institute of Bioregulation, Kyushu University
Jean-Sebastien Annicotte: Institut de Recherche en Cancérologie de Montpellier, INSERM U896
Lluis Fajas: Institut de Recherche en Cancérologie de Montpellier, INSERM U896
Marc Foretz: Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Inserm, U1016, Paris F-75014, France.
Francisco Verdeguer: Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Inserm, U1016, Paris F-75014, France.
Marco Pontoglio: Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Inserm, U1016, Paris F-75014, France.
Pascal Ferré: INSERM, Centre de Recherches des Cordeliers, UMR-S 872
Jean-Yves Scoazec: INSERM UMR865, Faculté Laennec, F–69372 Lyon Cedex 08, France.
Morris J. Birnbaum: University of Pennsylvania School of Medicine
Jean-Ehrland Ricci: Inserm, U895, Centre Méditerranéen de Médecine Moléculaire (C3M), équipe AVENIR
Mario Pende: Inserm, U845

Nature Communications, 2012, vol. 3, issue 1, 1-9

Abstract: Abstract Rapidly proliferating cells promote glycolysis in aerobic conditions, to increase growth rate. Expression of specific glycolytic enzymes, namely pyruvate kinase M2 and hexokinase 2, concurs to this metabolic adaptation, as their kinetics and intracellular localization favour biosynthetic processes required for cell proliferation. Intracellular factors regulating their selective expression remain largely unknown. Here we show that the peroxisome proliferator-activated receptor gamma transcription factor and nuclear hormone receptor contributes to selective pyruvate kinase M2 and hexokinase 2 gene expression in PTEN-null fatty liver. Peroxisome proliferator-activated receptor gamma expression, liver steatosis, shift to aerobic glycolysis and tumorigenesis are under the control of the Akt2 kinase in PTEN-null mouse livers. Peroxisome proliferator-activated receptor gamma binds to hexokinase 2 and pyruvate kinase M promoters to activate transcription. In vivo rescue of peroxisome proliferator-activated receptor gamma activity causes liver steatosis, hypertrophy and hyperplasia. Our data suggest that therapies with the insulin-sensitizing agents and peroxisome proliferator-activated receptor gamma agonists, thiazolidinediones, may have opposite outcomes depending on the nutritional or genetic origins of liver steatosis.

Date: 2012
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DOI: 10.1038/ncomms1667

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