2026-04-29T20:47:16Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/169482024-09-27T08:05:42Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Paredes, Ana author Justo-Mendez, Raquel author Jiménez-Blasco, Daniel author Nunez, Vanessa author Calero, Irene author Villalba-Orero, Maria author Alegre-Martí, Andrea author Fischer, Thierry author Gradillas, Ana author Sant'Anna, Viviane Aparecida Rodrigues author Were, Felipe author Huang, Zhiqiang author Hernansanz-Agustín, Pablo author Contreras, Carmen author Martinez, Fernando author Camafeita, Emilio author Vazquez, Jesus author Ruiz-Cabello, Jesus author Area-Gómez, Estela author Sanchez-Cabo, Fatima author Treuter, Eckardt author Bolaños, Juan Pedro author Estébanez-Perpiñá, Eva author Rupérez, Francisco Javier author Barbas, Coral author Enriquez, Jose Antonio author Ricote, Mercedes author 2023-06 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. Nature. 2023; 618(7964):365-373. 10.1038/s41586-023-06068-7 1476-4687 Nature 37225978 http://hdl.handle.net/20.500.12105/16948 γ-Linolenic acid in maternal milk drives cardiac metabolic maturation.