Inhibition of ATG3 ameliorates liver steatosis by increasing mitochondrial function
Por favor, use este identificador para citas ou ligazóns a este ítem:
http://hdl.handle.net/10347/27684
Ficheiros no ítem
Metadatos do ítem
Título: | Inhibition of ATG3 ameliorates liver steatosis by increasing mitochondrial function |
Autor/a: | Lima, Nátalia da Silva Fernández Fondevila Nóvoa Deaño, Eva María Buqué, Xabier Mercado Gómez, María Gallet, Sarah González Rellán, María Jesús Fernández Paz, Uxía Loyens, Anne García Vence, María Chantada Vázquez, María del Pilar Bravo López, Susana Belén Marañón Barnusell, Patricia Senra Viñas, Ana Escudero Pérez, Adriana Leiva Arjona, Magdalena Guallar Artal, Diana Fidalgo Pérez, Miguel Ángel Gomes, Pedro Claret, Marc Sabio Buzo, Guadalupe Varela Rey, Marta Cardoso Delgado, Teresa MONTERO VALLEJO, ROCIO Ampuero, Javier López Pérez, Miguel Antonio Diéguez González, Carlos Herrero, Laura Serra Cucurull, Dolors Schwaninger, Markus Prevot, Vincent Gallego-Durán, Rocío Romero-Gómez, Manuel IRUZUBIETA, PAULA Crespo García, Javier Martinez Chantar, Maria Luz García Monzón, Carmelo González-Rodríguez, Águeda Aspichueta, Patricia Nogueiras Pozo, Rubén |
Centro/Departamento: | Universidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas Universidade de Santiago de Compostela. Departamento de Bioquímica e Bioloxía Molecular Universidade de Santiago de Compostela. Departamento de Fisioloxía |
Palabras chave: | ATG3 | NAFLD | NASH | Sirtuin 1 | Lipid metabolism | Mitochondria | |
Data: | 2021 |
Editor: | Elsevier |
Cita bibliográfica: | Journal of Hepatology 76 (2022) 11-24. https://doi.org/10.1016/j.jhep.2021.09.008 |
Resumo: | Non-alcoholic fatty liver disease (NAFLD) is a major health threat in both developed and developing countries and is a precursor of the more advanced liver diseases, including non-alcoholic steatohepatitis (NASH), cirrhosis, and liver cancer. Currently, understanding the multiple and complex molecular pathways implicated in NAFLD onset and progression is a major priority. The transcription factor p63, which belongs to a family comprising p53, p63, and p73,1 is one of many factors that contributes to the development of liver steatosis. The role of p63 as a tumor suppressor and in cell maintenance and renewal is well studied, but we have recently reported that it is also relevant in the control of lipid metabolism.2 p63 encodes multiple isoforms that can be grouped into 2 categories; isoforms with an acidic transactivation domain (TA) and those without this domain (domain negative). The TAp63α isoform is elevated in the liver of animal models of NAFLD as well as in liver biopsies from obese patients with NAFLD. Furthermore, downregulation of p63α in the liver attenuates liver steatosis in diet-induced obese (DIO) mice, while the activation of TAp63α increases hepatic fat content, mediated by the activation of IKKβ and endoplasmic reticulum stress.2 A specialized form of autophagy that degrades lipid droplets, termed “lipophagy”, is a major pathway of lipid mobilization in hepatocytes. Lipophagy is elevated in hepatoma cells upon exposure to free fatty acids,3 and reduces the fatty acid load in mouse hepatocytes.4 Its impairment has been associated with the development of fatty liver and insulin resistance3,5; in contrast, the autophagic flux is increased during the activation of hepatic stellate cells.6 In the present study, we used an unbiased proteomics approach to gain insight into novel proteins modulating lipid metabolism in the liver of mice with genetic knockdown or overexpression of TAp63α. We found that autophagy-related gene 3 (ATG3) was upregulated by TAp63α activation and downregulated after p63α inhibition. ATG3 is elevated in several animal models of NAFLD and in the liver of patients with NAFLD. Genetic overexpression of ATG3 increased the lipid load in hepatocytes, while its repression alleviated TAp63α- and diet-induced steatosis. ATG3 exerted its role in lipid metabolism by regulating SIRT1 and mitochondrial function. Collectively, these findings identify ATG3 as a novel factor implicated in the development of steatosis |
Versión do editor: | https://doi.org/10.1016/j.jhep.2021.09.008 |
URI: | http://hdl.handle.net/10347/27684 |
DOI: | 10.1016/j.jhep.2021.09.008 |
E-ISSN: | 0168-8278 |
Dereitos: | © 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 (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
Coleccións
-
- BBM-Artigos [91]
- FIS-Artigos [114]
O ítem ten asociados os seguintes ficheiros de licenza:
A licenza do ítem descríbese como
© 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 (http://creativecommons.org/licenses/by-nc-nd/4.0/)
© 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 (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Items relacionados
Mostrando items relacionados por título, autor e materia.
-
Music education and didactic materials
Young, Susan; Marwa Abdelsalam Soleiman, Hassan; Romanelli, Guilherme; Rodrigues, Helena; Mariana, Miguel; Vences, Mariana; Santos, Maria; Rodrigues, Paulo Maria; Vicente Álvarez, Rosa María; Casal de la Fuente, Lucía; Cores Torres, Antia; Crespo Caride, Luis Miguel; Gillanders, Carol Jean; Romero Tabeayo, María Isabel; Tojeiro Pérez, Laura; Dosaiguas Canal, Marta; Pérez-Moreno, Jèssica; Pereira Ferreira, Vânia Marieta; Cunha, Daiane Solange Stoeberl da; Lima, Sonia Regina Albano de; Morales Fernandez, Ángela; Czmola, Halyne; Lucas Pitwak Menezes, Rosa; Lins, Mariane; Romanelli, Guilherme; López Vila, Leandro; Gillanders, Carol Jean; Martínez Delgado, Clara; Raposo Varela, María; Romanelli, Guilheme; Souza, Jusamara; Vicente Nicolás, Gregorio; Sánchez Marroquí, Judith; Arriaga, Cristina; De Alba, Baikune; Berbel Gómez, Noemy; Jaume-Adrover, Magdalena; Bermúdez de Castro, Juan José; Díaz-Gómez, Maravillas; Casal de la Fuente, Lucía; Echeverría de Miguel, Lucía; Asensio Arjona, Verónica; Cabedo-Mas, Alberto; Puerto-Sánchez, María-Jesús; Macián-González, Roberto; Moliner-Miravet, Lidón; López-Peláez Casellas, M.Paz; Martínez Morales, María; Moreno Montoro, María Isabel; Macián-González, Roberto; Tejada Giménez, Jesús; Mera Quintas, Eliseu; Asensio Arjona, Verónica; González Mediel, Olga; Totoricagüena, Maricel; Riaño, María Elena; Suárez-Canedo, Luis Román; Canceda, Silvia; Estavillo Morante, Mª del Carmen; Rodríguez-García, David; Pino Juste, Margarita R.; Pereira, Eliton Perpétuo Rosa; Buide del Real, Benito; Collantes Carollo, Francisco; Diz Otero, Mario; Llabrés González, Cristina; Vences, Mariana; Pereira, Ana Isabel; Rodrígues, Paulo María; Rodrigues, Paulo Ferreira; Rodrigues, Helena; Vicente Fernández, María; Vicente Álvarez, Rosa María; Mendive Zabaldica, Maria Soledad (Andavira, 2019) -
Unha enxeñeira ou científica en cada cole
Calvo Iglesias, Encina; Pérez Comuñas, María José; López Martínez, Paula; Aymerich López, María de la Inmaculada; Bao Varela, María del Carmen; Flores-Arias, María Teresa; García Fandiño, Rebeca; Costas Lago, Natalia; Rodríguez Malmierca, Mª José; Cernadas García, Eva; Hospido Quintana, Almudena; Roibás Cela, Laura; Ling Ling, Josefina F.; García Deibe, Ana María; Domínguez González, Raquel; Acevedo Arteaga, Laura; Pérez Meirás, María Dolores; Taboada Iglesias, María Jesús; López Lago, María Elena; Aguayo Lorenzo, Eva (Universidade de Vigo, Servizo de PublicaciónsUniversidade de Santiago de CompostelaUniversidade da Coruña, 2017)Nesta comunicación, presentamos o proxecto Unha enxeñeira ou científica en cada cole organizado pola Oficina de Igualdade de Xénero da Universidade de Santiago de Compostela (USC) en colaboración co Concello de Santiago ... -
Unha enxeñeira ou científica en cada cole
Calvo Iglesias, Encina; Pérez Comuñas, María José; López Martínez, Paula; Aymerich López, María de la Inmaculada; Bao Varela, María del Carmen; Flores Arias, María Teresa; García Fandiño, Rebeca; Costas Lago, Natalia; Rodríguez Malmierca, Mª José; Cernadas García, Eva; Hospido Quintana, Almudena; Roibás Cela, Laura; Ling Ling, Josefina F.; García Deibe, Ana María; Domínguez González, Raquel; Acevedo Arteaga, Laura; Pérez Meirás, María Dolores; Taboada Iglesias, María Jesús; López Lago, María Elena; Aguayo Lorenzo, Eva (2017-07)Nesta comunicación, presentamos o proxecto Unha enxeñeira ou científica en cada cole organizado pola Oficina de Igualdade de Xénero da Universidade de Santiago de Compostela (USC) en colaboración co Concello de Santiago ...