Activation of a HIF1alpha-PPARgamma axis underlies the integration of glycolytic and lipid anabolic pathways in pathologic cardiac hypertrophy.

Détails

ID Serval
serval:BIB_8A248426FB79
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Activation of a HIF1alpha-PPARgamma axis underlies the integration of glycolytic and lipid anabolic pathways in pathologic cardiac hypertrophy.
Périodique
Cell Metabolism
Auteur(s)
Krishnan J., Suter M., Windak R., Krebs T., Felley A., Montessuit C., Tokarska-Schlattner M., Aasum E., Bogdanova A., Perriard E., Perriard J.C., Larsen T., Pedrazzini T., Krek W.
ISSN
1932-7420[electronic]
Statut éditorial
Publié
Date de publication
2009
Volume
9
Numéro
6
Pages
512-524
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
Development of cardiac hypertrophy and progression to heart failure entails profound changes in myocardial metabolism, characterized by a switch from fatty acid utilization to glycolysis and lipid accumulation. We report that hypoxia-inducible factor (HIF)1alpha and PPARgamma, key mediators of glycolysis and lipid anabolism, respectively, are jointly upregulated in hypertrophic cardiomyopathy and cooperate to mediate key changes in cardiac metabolism. In response to pathologic stress, HIF1alpha activates glycolytic genes and PPARgamma, whose product, in turn, activates fatty acid uptake and glycerolipid biosynthesis genes. These changes result in increased glycolytic flux and glucose-to-lipid conversion via the glycerol-3-phosphate pathway, apoptosis, and contractile dysfunction. Ventricular deletion of Hif1alpha in mice prevents hypertrophy-induced PPARgamma activation, the consequent metabolic reprogramming, and contractile dysfunction. We propose a model in which activation of the HIF1alpha-PPARgamma axis by pathologic stress underlies key changes in cell metabolism that are characteristic of and contribute to common forms of heart disease.
Mots-clé
Animals, Apoptosis, Cardiomegaly/metabolism, Fatty Acids/metabolism, Glycolysis, Hypoxia-Inducible Factor 1, alpha Subunit/genetics, Hypoxia-Inducible Factor 1, alpha Subunit/metabolism, Lipid Metabolism, Mice, Mice, Knockout, Myocytes, Cardiac/metabolism, PPAR gamma/genetics, PPAR gamma/metabolism, Phosphoric Monoester Hydrolases/metabolism, Up-Regulation, Von Hippel-Lindau Tumor Suppressor Protein/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
03/02/2010 18:21
Dernière modification de la notice
08/05/2019 21:38
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