dc.contributor.author | Da Silva Lima, Natalia | |
dc.contributor.author | Fondevila, Marcos F. | |
dc.contributor.author | Novoa, Eva | |
dc.contributor.author | Buqué García, Xabier | |
dc.contributor.author | Mercado Gómez, María | |
dc.contributor.author | Gallet, Sarah | |
dc.contributor.author | González Rellán, María Jesús | |
dc.contributor.author | Fernández, Uxia | |
dc.contributor.author | Loyens, Anne | |
dc.contributor.author | García Vence, María | |
dc.contributor.author | Chantada Vázquez, María del Pilar | |
dc.contributor.author | Bravo López, Susana Belén | |
dc.contributor.author | Marañón, Patricia | |
dc.contributor.author | Senra, Ana | |
dc.contributor.author | Escudero González, Adriana | |
dc.contributor.author | Leiva, Magdalena | |
dc.contributor.author | Guallar, Diana | |
dc.contributor.author | Fidalgo, Miguel | |
dc.contributor.author | Gomes, Pedro | |
dc.contributor.author | Claret, Marc | |
dc.contributor.author | Sabio, Guadalupe | |
dc.contributor.author | Varela Rey, Marta | |
dc.contributor.author | Cardoso Delgado, Teresa de Jesús | |
dc.contributor.author | Montero Vallejo, Rocío | |
dc.contributor.author | Ampuero Herrojo, Javier | |
dc.contributor.author | López, Miguel | |
dc.contributor.author | Diéguez González, Carlos | |
dc.contributor.author | Herrero, Laura | |
dc.contributor.author | Serra, Dolors | |
dc.contributor.author | Schwaninger, Markus | |
dc.contributor.author | Prevot, Vincent | |
dc.contributor.author | Gallego Durán, Rocío | |
dc.contributor.author | Romero Gómez, Manuel | |
dc.contributor.author | Iruzubieta, Paula | |
dc.contributor.author | Crespo, Javier | |
dc.contributor.author | Martínez Chantar, María Luz | |
dc.contributor.author | García Monzón, Carmelo | |
dc.contributor.author | González Rodríguez, Águeda | |
dc.contributor.author | Aspichueta Celaá, Patricia | |
dc.contributor.author | Nogueiras Pozo, Rubén | |
dc.date.accessioned | 2022-01-10T10:55:28Z | |
dc.date.available | 2022-01-10T10:55:28Z | |
dc.date.issued | 2022-01 | |
dc.identifier.citation | Journal of hepatology 76(1) : 11-24 (2022) | es_ES |
dc.identifier.issn | 0168-8278 | |
dc.identifier.issn | 1600-0641 | |
dc.identifier.uri | http://hdl.handle.net/10810/54853 | |
dc.description.abstract | [EN]Background & Aims: Autophagy-related gene 3 (ATG3) is an enzyme mainly known for its actions in the LC3 lipidation process, which is essential for autophagy. Whether ATG3 plays a role in lipid metabolism or contributes to non-alcoholic fatty liver disease (NAFLD) remains unknown.
Methods: By performing proteomic analysis on livers from mice with genetic manipulation of hepatic p63, a regulator of fatty acid metabolism, we identified ATG3 as a new target downstream of p63. ATG3 was evaluated in liver samples from patients with NAFLD. Further, genetic manipulation of ATG3 was performed in human hepatocyte cell lines, primary hepatocytes and in the livers of mice.
Results: ATG3 expression is induced in the liver of animal models and patients with NAFLD (both steatosis and nonalcoholic steatohepatitis) compared with those without liver disease. Moreover, genetic knockdown of ATG3 in mice and human hepatocytes ameliorates p63-and diet-induced steatosis, while its overexpression increases the lipid load in hepatocytes. The inhibition of hepatic ATG3 improves fatty acid metabolism by reducing c-Jun N-terminal protein kinase 1 (JNK1), which increases sirtuin 1 (SIRT1), carnitine palmitoyltransferase 1a (CPT1a), and mitochondrial function. Hepatic knockdown of SIRT1 and CPT1a blunts the effects of ATG3 on mitochondrial activity. Unexpectedly, these effects are independent of an autophagic action. Conclusions: Collectively, these findings indicate that ATG3 is a novel protein implicated in the development of steatosis.
Lay summary: We show that autophagy-related gene 3 (ATG3) contributes to the progression of non-alcoholic fatty liver disease | es_ES |
dc.description.sponsorship | This work has been supported by grants from FEDER/Ministerio de Ciencia, Innovacion y Universidades-Agencia Estatal de Investigacion (PA: RTI2018-095134-B-100; DS and LH: SAF2017-83813-C3-1-R; MLMC: RTC2019-007125-1; CD: BFU2017-87721; ML: RTI2018-101840-B-I0 0; GS; PID2019-104399RB-I0 0; RN: RTI2018-099413-B-I0 0 and RED2018-102379-T; MLMC: SAF2017-87301-R; TCD: RTI2018-096759-A-10 0) , FEDER/Instituto de Salud Carlos III (AGR: PI19/00123) , Xunta de Galicia (ML: 2016-PG068; RN: 2015-CP080 and 2016-PG057) , Fundacion BBVA (RN, GS and MLM) , Proyectos Investigacion en Salud (MLMC: DTS20/00138) , Sistema Universitario Vasco (PA: IT971-16) ; Fun-dacion Atresmedia (ML and RN) , Fundacion La Caixa (M.L., R.N. and M.C.) , Gilead Sciences International Research Scholars Pro-gram in Liver Disease (MVR) , Marato TV3 Foundation (DS: 201627) , Government of Catalonia (DS: 2017SGR278) and Euro-pean Foundation for the Study of Diabetes (RN and GS) . This research also received funding from the European Community's H2020 Framework Programme (ERC Synergy Grant-2019-WATCH-810331, to RN, VP and MS) . Centro de Investigacion Biomedica en Red (CIBER) de Fisiopatologia de la Obesidad y Nutricion (CIBERobn) , Centro de Investigacion Biomedica en Red (CIBER) de Enfermedades Hepaticas y Digestivas (CIBERehd) and CIBER de Diabetes y Enfermedades Metabolicas Asociadas (CIBERdem) . CIBERobn, CIBERehd and CIBERdem are initiatives of the Instituto de Salud Carlos III (ISCIII) of Spain which is supported by FEDER funds. We thank MINECO for the Severo Ochoa Excellence Accreditation to CIC bioGUNE (SEV-2016-064 4) . | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Elsevier | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/SAF2017-83813-C3-1-R | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/BFU2017-87721 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/SAF2017-87301-R | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICIU/RTI2018-095134-B-100 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICIU/RTI2018-101840-B-I0 0 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICIU/RTI2018-099413-B-I0 0 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICIU/RED2018-102379-T | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICIU/RTI2018-096759-A-10 0 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/RTC2019-007125-1 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/PID2019-104399RB-I0 0 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.subject | ATG3 | es_ES |
dc.subject | sirtuin 1 | es_ES |
dc.subject | lipid metabolism | es_ES |
dc.subject | NAFLD | es_ES |
dc.subject | NASH | es_ES |
dc.subject | mitochondria | es_ES |
dc.title | Inhibition of ATG3 ameliorates liver steatosis by increasing mitochondrial function | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | © 2021 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver. This is an open access article under the CC BY-NC-ND license | es_ES |
dc.rights.holder | Atribución-NoComercial-SinDerivadas 3.0 España | * |
dc.relation.publisherversion | https://www.sciencedirect.com/science/article/pii/S0168827821020389?via%3Dihub | es_ES |
dc.identifier.doi | 10.1016/j.jhep.2021.09.008 | |
dc.departamentoes | Fisiología | es_ES |
dc.departamentoeu | Fisiologia | es_ES |