PPARγ Contributes to PKM2 and HK2 Expression in Fatty Liver

Overview

Journal Nat Commun

Specialty Biology

Date 2012 Feb 16

PMID 22334075

Citations 98

Authors

Ganna Panasyuk

Catherine Espeillac

Celine Chauvin

Ludivine A Pradelli

Yasuo Horie

Akira Suzuki

Jean-Sebastien Annicotte

Lluis Fajas

Marc Foretz

Francisco Verdeguer

Marco Pontoglio

Pascal Ferre

Jean-Yves Scoazec

Morris J Birnbaum

Jean-Ehrland Ricci

Mario Pende

Affiliations

Soon will be listed here.

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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