Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/13343
Título
Activation of amino acid metabolic program in cardiac HIF1-alpha-deficient mice.
Autor(es)
Menendez-Montes, Ivan | Escobar, Beatriz CNIC | Gomez, Manuel J CNIC | Albendea-Gomez, Teresa | Palacios, Beatriz CNIC | Bonzon-Kulichenko, Elena CNIC | Izquierdo-Garcia, Jose Luis | Alonso, Ana Vanessa | Ferrarini, Alessia CNIC | Jimenez-Borreguero, Luis J CNIC | Ruiz-Cabello, Jesus CNIC | Vazquez, Jesus CNIC | Martin-Puig, Silvia CNIC
Fecha de publicación
2021-02-19
Cita
iScience. 2021; 24(2):102124
Idioma
Inglés
Tipo de documento
journal article
Resumen
HIF1-alpha expression defines metabolic compartments in the developing heart, promoting glycolytic program in the compact myocardium and mitochondrial enrichment in the trabeculae. Nonetheless, its role in cardiogenesis is debated. To assess the importance of HIF1-alpha during heart development and the influence of glycolysis in ventricular chamber formation, herein we generated conditional knockout models of Hif1a in Nkx2.5 cardiac progenitors and cardiomyocytes. Deletion of Hif1a impairs embryonic glycolysis without influencing cardiomyocyte proliferation and results in increased mitochondrial number and transient activation of amino acid catabolism together with HIF2α and ATF4 upregulation by E12.5. Hif1a mutants display normal fatty acid oxidation program and do not show cardiac dysfunction in the adulthood. Our results demonstrate that cardiac HIF1 signaling and glycolysis are dispensable for mouse heart development and reveal the metabolic flexibility of the embryonic myocardium to consume amino acids, raising the potential use of alternative metabolic substrates as therapeutic interventions during ischemic events.
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