PPAR gamma contributes to PKm2 and HK2 expressionin fatty liver

摘要

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 favourbiosynthetic processes required for cell proliferation. Intracellular factors regulating theirselective expression remain largely unknown. Here we show that the peroxisome proliferatoractivated receptor gamma transcription factor and nuclear hormone receptor contributesto selective pyruvate kinase m2 and hexokinase 2 gene expression in PTEN-null fatty liver.Peroxisome proliferator-activated receptor gamma expression, liver steatosis, shift to aerobicglycolysis 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 kinasem promoters to activate transcription. In vivo rescue of peroxisome proliferator-activatedreceptor gamma activity causes liver steatosis, hypertrophy and hyperplasia. our data suggestthat therapies with the insulin-sensitizing agents and peroxisome proliferator-activatedreceptor gamma agonists, thiazolidinediones, may have opposite outcomes depending on thenutritional or genetic origins of liver steatosis.