Mostrar el registro sencillo del ítem
dc.contributor.author | Plata-Gómez, Ana Belén | |
dc.contributor.author | de Prado-Rivas, Lucía | |
dc.contributor.author | Sanz, Alba | |
dc.contributor.author | Deleyto-Seldas, Nerea | |
dc.contributor.author | García, Fernando | |
dc.contributor.author | de la Calle Arregui, Celia | |
dc.contributor.author | Silva, Camila | |
dc.contributor.author | Caleiras, Eduardo | |
dc.contributor.author | Graña-Castro, Osvaldo | |
dc.contributor.author | Piñeiro-Yáñez, Elena | |
dc.contributor.author | Krebs, Joseph | |
dc.contributor.author | Leiva-Vega, Luis | |
dc.contributor.author | Muñoz, Javier | |
dc.contributor.author | Jain, Ajay | |
dc.contributor.author | Sabio, Guadalupe | |
dc.contributor.author | Efeyan, Alejo | |
dc.date.accessioned | 2024-07-03T14:16:41Z | |
dc.date.available | 2024-07-03T14:16:41Z | |
dc.date.issued | 2024-03-18 | |
dc.identifier.citation | Nat Commun. 2024 Mar 18;15(1):1878. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/20034 | |
dc.description.abstract | The metabolic functions of the liver are spatially organized in a phenomenon called zonation, linked to the differential exposure of portal and central hepatocytes to nutrient-rich blood. The mTORC1 signaling pathway controls cellular metabolism in response to nutrients and insulin fluctuations. Here we show that simultaneous genetic activation of nutrient and hormone signaling to mTORC1 in hepatocytes results in impaired establishment of postnatal metabolic and zonal identity of hepatocytes. Mutant hepatocytes fail to upregulate postnatally the expression of Frizzled receptors 1 and 8, and show reduced Wnt/β-catenin activation. This defect, alongside diminished paracrine Wnt2 ligand expression by endothelial cells, underlies impaired postnatal maturation. Impaired zonation is recapitulated in a model of constant supply of nutrients by parenteral nutrition to piglets. Our work shows the role of hepatocyte sensing of fluctuations in nutrients and hormones for triggering a latent metabolic zonation program. | es_ES |
dc.description.sponsorship | We thank CNIO Histopathology, Animal Facility and Genomics Core Units for excellent technical support. The RETOS projects Program of Spanish Ministry of Science, Innovation and Universities, Spanish State Research Agency, cofunded by the European Regional Development Fund (grants PID2019-104012RB-I00 and PID2022-136413OB-I00), EUH2020 Program (ERC-2014-STG-638891), Excellence Network Grant from MICIU/AEI (SAF2016-81975-REDT), Spanish Association Against Cancer Research Scientific Foundation Laboratory Grant, Beca de Investigació n en Oncologi ́ a Olivia Roddom, FERO Grant for Research in Oncology and funding from LaCaixa Banking Foundation (LCF/PR/HR21/ 0046) (to A.E.). The work in the lab of J.M. is supported by European Proteomics Infrastructure Consortium providing access (EPIC-XS): Project number 823839. A.B.P.G., L.d.P.R., N.D.S. and C.D.C.A. are recipients of Ayudas de contratos predoctorales para la formación de doctores from MICIU/AEI (BES-2017 − 081381, PRE-2019-090891, BES2016-077410, BES-2015-073776). A.E. is an EMBO Young Investigator. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Nature Publishing Group | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject.mesh | Endothelial Cells | es_ES |
dc.subject.mesh | Liver | es_ES |
dc.subject.mesh | Swine | es_ES |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Mechanistic Target of Rapamycin Complex 1 | es_ES |
dc.subject.mesh | Hepatocytes | es_ES |
dc.subject.mesh | Signal Transduction | es_ES |
dc.subject.mesh | Insulin | es_ES |
dc.title | Hepatic nutrient and hormone signaling to mTORC1 instructs the postnatal metabolic zonation of the liver. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 38499523 | es_ES |
dc.format.volume | 15 | es_ES |
dc.format.number | 1 | es_ES |
dc.format.page | 1878 | es_ES |
dc.identifier.doi | 10.1038/s41467-024-46032-1 | es_ES |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | es_ES |
dc.contributor.funder | Unión Europea. Comisión Europea. European Research Council (ERC) | es_ES |
dc.contributor.funder | Fundación La Caixa | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 2041-1723 | es_ES |
dc.relation.publisherversion | 10.1038/s41467-024-46032-1 | es_ES |
dc.identifier.journal | Nature communications | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Papel de las quinasas activadas por el estrés en el desarrollo de enfermedades cardiovasculares, diabetes y cáncer | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/ERC-2014-STG-638891 | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PID2019-104012RB-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PID2022-136413OB-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/SAF2016-81975-REDT | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/LCF/PR/HR21/0046 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/BES-2017−081381 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PRE-2019-090891 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/BES2016-077410 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/BES-2015-073776 | es_ES |