Portal de investigación
gamma-Linolenic acid in maternal milk drives cardiac metabolic maturation
Autores de IBSAL
Autores ajenos a IBSAL
- Paredes, A
- Justo-Mendez, R
- Nunez, V
- Calero, I
- Villalba-Orero, M
- Alegre-Marti, A
- Fischer, T
- Gradillas, A
- Sant'Anna, VAR
- Were, F
- Huang, ZQ
- Hernansanz-Agustin, P
- Contreras, C
- Martinez, F
- Camafeita, E
- Vazquez, J
- Ruiz-Cabello, J
- Area-Gomez, E
- Sanchez-Cabo, F
- Treuter, E
- Estebanez-Perpina, E
- Ruperez, FJ
- Barbas, C
- Enriquez, JA
- Ricote, M
Grupos
Abstract
Birth presents a metabolic challenge to cardiomyocytes as they reshape fuel preference from glucose to fatty acids for postnatal energy production(1,2). This adaptation is triggered in part by post-partum environmental changes(3), but the molecules orchestrating cardiomyocyte maturation remain unknown. Here we show that this transition is coordinated by maternally supplied ?-linolenic acid (GLA), an 18:3 omega-6 fatty acid enriched in the maternal milk. GLA binds and activates retinoid X receptors(4) (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.
Datos de la publicación
- ISSN/ISSNe:
- 0028-0836, 1476-4687
- Tipo:
- Article
- Páginas:
- 365-365
NATURE NATURE PUBLISHING GROUP
Citas Recibidas en Web of Science: 3
Documentos
- No hay documentos
Filiaciones
Keywords
- RETINOID-X-RECEPTORS; POLYUNSATURATED FATTY-ACIDS; RXR-ALPHA; PEPTIDE IDENTIFICATION; SUBSTRATE UTILIZATION; READ ALIGNMENT; WORKING HEARTS; ATP PRODUCTION; BREAST-MILK; OXIDATION
Campos de estudio
Financiación
Proyectos asociados
3. Frailty and Aging. 3.1. Healthy aging biological mechanisms oriented to the maintenance of functional autonomy and mechanisms leading to frailty and disability. CICERFES
Investigador Principal: Juan Pedro Bolaños Hernández
CB16/10/00282 . Instituto de Salud Carlos III . 2017
Cita
Paredes A,Justo R,Jimenez D,Nunez V,Calero I,Villalba M,Alegre A,Fischer T,Gradillas A,Sant'Anna V,Were F,Huang ZQ,Hernansanz P,Contreras C,Martinez F,Camafeita E,Vazquez J,Ruiz J,Area E,Sanchez F,Treuter E,Bolanos JP,Estebanez E,Ruperez FJ,Barbas C,Enriquez JA,Ricote M. gamma-Linolenic acid in maternal milk drives cardiac metabolic maturation. Nature. 2023. 618. (7964):p. 365-365. IF:50,500. (1).