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PPARγ contributes to PKM2 and HK2 expression in fatty liver.

Authors
  • 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
  • Mario Pende
Identifiers
DOI: 10.1038/ncomms1667
Source
CdV-UPMC
License
Unknown

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.

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