RT Journal Article
T1 γ-Linolenic acid in maternal milk drives cardiac metabolic maturation
A1 Paredes, Ana
A1 Villalba Orero, María
A1 Ruiz-Cabello Osuna, Jesús
A1 Ricote, Mercedes
AB 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.
SN 0028-0836
YR 2023
FD 2023
LK https://hdl.handle.net/20.500.14352/97794
UL https://hdl.handle.net/20.500.14352/97794
LA eng
NO Paredes, A., Justo-Méndez, R., Jiménez-Blasco, D. et al. γ-Linolenic acid in maternal milk drives cardiac metabolic maturation. Nature 618, 365–373 (2023). https://doi.org/10.1038/s41586-023-06068-7
NO Junta de Castilla y León
NO European Commission
NO Ministerio de Ciencia e Innovación (España)
NO Instituto de Salud Carlos III
NO Airbus Defense and Space
NO Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Brasil)
NO Swedish Cancer Society
NO Novo Nordisk Foundation
NO Swedish Research Council
DS Docta Complutense
RD 6 abr 2025