dc.contributor.author | Paredes, Ana | |
dc.contributor.author | Justo-Mendez, Raquel | |
dc.contributor.author | Jiménez-Blasco, Daniel | |
dc.contributor.author | Nunez, Vanessa | |
dc.contributor.author | Calero, Irene | |
dc.contributor.author | Villalba-Orero, Maria | |
dc.contributor.author | Alegre-Martí, Andrea | |
dc.contributor.author | Fischer, Thierry | |
dc.contributor.author | Gradillas, Ana | |
dc.contributor.author | Sant'Anna, Viviane Aparecida Rodrigues | |
dc.contributor.author | Were, Felipe | |
dc.contributor.author | Huang, Zhiqiang | |
dc.contributor.author | Hernansanz-Agustín, Pablo | |
dc.contributor.author | Contreras, Carmen | |
dc.contributor.author | Martinez, Fernando | |
dc.contributor.author | Camafeita, Emilio | |
dc.contributor.author | Vazquez, Jesus | |
dc.contributor.author | Ruiz-Cabello, Jesus | |
dc.contributor.author | Area-Gómez, Estela | |
dc.contributor.author | Sanchez-Cabo, Fatima | |
dc.contributor.author | Treuter, Eckardt | |
dc.contributor.author | Bolaños, Juan Pedro | |
dc.contributor.author | Estébanez-Perpiñá, Eva | |
dc.contributor.author | Rupérez, Francisco Javier | |
dc.contributor.author | Barbas, Coral | |
dc.contributor.author | Enriquez, Jose Antonio | |
dc.contributor.author | Ricote, Mercedes | |
dc.date.accessioned | 2024-01-12T09:27:40Z | |
dc.date.available | 2024-01-12T09:27:40Z | |
dc.date.issued | 2023-06 | |
dc.identifier.citation | Nature. 2023; 618(7964):365-373. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/16948 | |
dc.description.abstract | Birth presents a metabolic challenge to cardiomyocytes as they reshape fuel preference from glucose to fatty acids for postnatal energy production1,2. This adaptation is triggered in part by post-partum environmental changes3, but the molecules orchestrating cardiomyocyte maturation remain unknown. Here we show that this transition is coordinated by maternally supplied γ-linolenic acid (GLA), an 18:3 omega-6 fatty acid enriched in the maternal milk. GLA binds and activates retinoid X receptors4 (RXRs), ligand-regulated transcription factors that are expressed in cardiomyocytes from embryonic stages. Multifaceted genome-wide analysis revealed that the lack of RXR in embryonic cardiomyocytes caused an aberrant chromatin landscape that prevented the induction of an RXR-dependent gene expression signature controlling mitochondrial fatty acid homeostasis. The ensuing defective metabolic transition featured blunted mitochondrial lipid-derived energy production and enhanced glucose consumption, leading to perinatal cardiac dysfunction and death. Finally, GLA supplementation induced RXR-dependent expression of the mitochondrial fatty acid homeostasis signature in cardiomyocytes, both in vitro and in vivo. Thus, our study identifies the GLA-RXR axis as a key transcriptional regulatory mechanism underlying the maternal control of perinatal cardiac metabolism. | es_ES |
dc.language.iso | eng | es_ES |
dc.type.hasVersion | AM | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject.mesh | Fatty Acids | es_ES |
dc.subject.mesh | gamma-Linolenic Acid | es_ES |
dc.subject.mesh | Glucose | es_ES |
dc.subject.mesh | Heart | es_ES |
dc.subject.mesh | Milk, Human | es_ES |
dc.subject.mesh | Female | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Infant, Newborn | es_ES |
dc.subject.mesh | Pregnancy | es_ES |
dc.subject.mesh | Chromatin | es_ES |
dc.subject.mesh | Gene Expression Regulation | es_ES |
dc.subject.mesh | Homeostasis | es_ES |
dc.subject.mesh | In Vitro Techniques | es_ES |
dc.subject.mesh | Mitochondria | es_ES |
dc.subject.mesh | Myocytes, Cardiac | es_ES |
dc.subject.mesh | Retinoid X Receptors | es_ES |
dc.subject.mesh | Transcription Factors | es_ES |
dc.title | γ-Linolenic acid in maternal milk drives cardiac metabolic maturation. | es_ES |
dc.type | research article | es_ES |
dc.rights.license | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.identifier.pubmedID | 37225978 | es_ES |
dc.format.volume | 618 | es_ES |
dc.format.number | 7964 | es_ES |
dc.format.page | 365 | es_ES |
dc.identifier.doi | 10.1038/s41586-023-06068-7 | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1476-4687 | es_ES |
dc.identifier.journal | Nature | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Genética Funcional del Sistema de Fosforilación Oxidativa | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.rights.accessRights | open access | es_ES |