by Menendez-Montes, Ivan, Escobar, Beatriz, Gomez, Manuel J., Albendea-Gomez, Teresa, Palacios, Beatriz, Bonzon-Kulichenko, Elena, Izquierdo-Garcia, Jose Luis, Alonso, Ana Vanessa, Ferrarini, Alessia, Jimenez-Borreguero, Luis Jesus, Ruiz-Cabello, Jesus, Vázquez, Jesus and Martin-Puig, Silvia
Abstract:
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 HIF2$alpha$ 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.
Reference:
Activation of amino acid metabolic program in cardiac HIF1-alpha-deficient mice (Menendez-Montes, Ivan, Escobar, Beatriz, Gomez, Manuel J., Albendea-Gomez, Teresa, Palacios, Beatriz, Bonzon-Kulichenko, Elena, Izquierdo-Garcia, Jose Luis, Alonso, Ana Vanessa, Ferrarini, Alessia, Jimenez-Borreguero, Luis Jesus, Ruiz-Cabello, Jesus, Vázquez, Jesus and Martin-Puig, Silvia), In iScience, volume 24, 2021.
Bibtex Entry:
@article{menendez-montes_activation_2021,
	title = {Activation of amino acid metabolic program in cardiac {HIF1}-alpha-deficient mice},
	volume = {24},
	issn = {2589-0042},
	doi = {10.1016/j.isci.2021.102124},
	abstract = {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 HIF2$alpha$ 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.},
	language = {eng},
	number = {2},
	journal = {iScience},
	author = {Menendez-Montes, Ivan and Escobar, Beatriz and Gomez, Manuel J. and Albendea-Gomez, Teresa and Palacios, Beatriz and Bonzon-Kulichenko, Elena and Izquierdo-Garcia, Jose Luis and Alonso, Ana Vanessa and Ferrarini, Alessia and Jimenez-Borreguero, Luis Jesus and Ruiz-Cabello, Jesus and V{'a}zquez, Jesus and Martin-Puig, Silvia},
	month = feb,
	year = {2021},
	pmid = {33665549},
	pmcid = {PMC7900219},
	keywords = {Animal Physiology, Biological Sciences, Cellular Physiology, Developmental Biology},
	pages = {102124},
	file = {Full Text:/Users/jruizcabello/Zotero/storage/VVC87WQ7/Menendez-Montes et al. - 2021 - Activation of amino acid metabolic program in card.pdf:application/pdf},
}