摘要：SummaryHIF1-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 ofHif1ain Nkx2.5 cardiac progenitors and cardiomyocytes. Deletion ofHif1aimpairs 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.Hif1amutants 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.Graphical abstractDisplay OmittedHighlights•Loss of cardiacHif1adoes not preclude heart development or cardiac function•EmbryonicHif1a-deficient hearts transiently upregulate amino acid catabolism•Amino acid catabolism activation sustains heart growth in the absence of glycolysis•HIF2α and ATF4 are transiently upregulated in the developing heart uponHif1alossAnimal Physiology; Biological Sciences; Cellular Physiology; Developmental Biology
