Published 2012 | Version v1
Journal article

PPARĪ³ contributes to PKM2 and HK2 expression in fatty liver

Others:
Centre de recherche Croissance et signalisation (UMR_S 845) ; UniversitƩ Paris Descartes - Paris 5 (UPD5)-Institut National de la SantƩ et de la Recherche MƩdicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Centre mƩditerranƩen de mƩdecine molƩculaire (C3M) ; UniversitƩ Nice Sophia Antipolis (1965 - 2019) (UNS) ; COMUE UniversitƩ CƓte d'Azur (2015-2019) (COMUE UCA)-COMUE UniversitƩ CƓte d'Azur (2015-2019) (COMUE UCA)-Institut National de la SantƩ et de la Recherche MƩdicale (INSERM)-UniversitƩ CƓte d'Azur (UCA)
Akita University
Kyushu University [Fukuoka]
Institut de recherche en cancƩrologie de Montpellier (IRCM - U896 Inserm - UM1) ; UniversitƩ Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la SantƩ et de la Recherche MƩdicale (INSERM)-UniversitƩ de Montpellier (UM)
Institut Cochin (IC UM3 (UMR 8104 / U1016)) ; UniversitƩ Paris Descartes - Paris 5 (UPD5)-Institut National de la SantƩ et de la Recherche MƩdicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Pathologies nutritionnelles et mĆ©taboliques : obĆ©sitĆ© et diabĆØte ; UniversitĆ© Pierre et Marie Curie - Paris 6 (UPMC)-IFR58-Institut National de la SantĆ© et de la Recherche MĆ©dicale (INSERM)
Centre de Recherche des Cordeliers (CRC (UMR_S 872)) ; UniversitƩ Pierre et Marie Curie - Paris 6 (UPMC)-UniversitƩ Paris Descartes - Paris 5 (UPD5)-Institut National de la SantƩ et de la Recherche MƩdicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Centre de Recherche en CancƩrologie de Lyon (UNICANCER/CRCL) ; Centre LƩon BƩrard [Lyon]-UniversitƩ Claude Bernard Lyon 1 (UCBL) ; UniversitƩ de Lyon-UniversitƩ de Lyon-Institut National de la SantƩ et de la Recherche MƩdicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Tumeurs endocrines digestives : mĆ©canismes de la tumorigenĆØse et de la progression tumorale ; UniversitĆ© Claude Bernard Lyon 1 (UCBL) ; UniversitĆ© de Lyon-UniversitĆ© de Lyon-Institut National de la SantĆ© et de la Recherche MĆ©dicale (INSERM)
University of Pennsylvania [Philadelphia]
This work was supported by grants from the European Research Council, from Fondation de la Recherche Medicale (DEQ20061107956) and from Fondation Schlumberger pour l'Education et la Recherche to M.P., and from the Association pour la Recherche sur le Cancer to M.P. and J.-E.R. L.A.P received a fellowship from the RĆ©gion Provence-Alpes-Cote-d'Azur and INSERM, C.E. from Ministere de Recherche et Technologies and from Fondation de la Recherche Medicale.
We are grateful to the members of INSERM-U845 for support, and to David Sabatini, Stefano Fumagalli, Benoit Viollet, Fabienne Foufelle, Renaud Dentin, Pascal Pineau, Isabelle AndrƩ-Schmutz, Olivier Danos and Anne Dejean for helpful discussions and sharing reagents. We thank Sophie Berissi, Dominique Chretien and Sylvie Fabrega for technical support.

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Description

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.

Abstract

International audience

Additional details

Created:
December 4, 2022
Modified:
November 29, 2023