Neddylation inhibition ameliorates steatosis in NAFLD by boosting hepatic fatty acid oxidation via DEPTOR-mTOR axis
View/ Open
Date
2021-06-18Author
Serrano Maciá, Marina
Simon, Jorge
González Rellán, María Jesús
Azkargorta, Mikel
Goikoetxea Usandizaga, Naroa
Lopitz Otsoa, Fernando
Saenz de Urturi Indart, Diego
Rodríguez Agudo, Rubén
Lachiondo Ortega, Sofía
Mercado Gómez, María
Gutiérrez de Juan, Virginia
Bizkarguenaga, Maider
Fernández Ramos, David
Baselli, Guido A.
Valenti, Luca
Iruzubieta, Paula
Crespo, Javier
Villa, Erica
Marin, José J. G.
Aspichueta Celaá, Patricia
Sutherland, James D.
Barrio Olano, María Rosa
Elortza, Felix
Xirodimas, Dimitri
Nogueiras Pozo, Rubén
Delgado, Teresa C.
Metadata
Show full item record
Molecular Metabolism 53 : (2021) // Article ID 101275
Abstract
[EN] Objective: Neddylation is a druggable and reversible ubiquitin-like post-translational modification upregulated in many diseases, including liver
fibrosis, hepatocellular carcinoma, and more recently, non-alcoholic fatty liver disease (NAFLD). Herein, we propose to address the effects of
neddylation inhibition and the underlying mechanisms in pre-clinical models of NAFLD.
Methods: Hepatic neddylation measured by immunohistochemical analysis and NEDD8 serum levels measured by ELISA assay were evaluated
in NAFLD clinical and pre-clinical samples. The effects of neddylation inhibition by using a pharmacological small inhibitor, MLN4924, or molecular
approaches were assessed in isolated mouse hepatocytes and pre-clinical mouse models of diet-induced NAFLD, male adult C57BL/6
mice, and the AlfpCre transgenic mice infected with AAV-DIO-shNedd8.
Results: Neddylation inhibition reduced lipid accumulation in oleic acid-stimulated mouse primary hepatocytes and ameliorated liver steatosis,
preventing lipid peroxidation and inflammation in the mouse models of diet-induced NAFLD. Under these conditions, increased Deptor levels and
the concomitant repression of mTOR signaling were associated with augmented fatty acid oxidation and reduced lipid content. Moreover, Deptor
silencing in isolated mouse hepatocytes abolished the anti-steatotic effects mediated by neddylation inhibition. Finally, serum NEDD8 levels
correlated with hepatic neddylation during the disease progression in the clinical and pre-clinical models
Except where otherwise noted, this item's license is described as ©2021 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4 (cc by-nc-nd)
Related items
Showing items related by title, author, creator and subject.
-
Diseño del Practicum del Grado en Enfermería - Practicumaren diseinua Erizaintzako Graduan
Uranga Iturrioz, María José; Gil Molina, Pilar ; Alberdi Erice, María José; Barandiaran Lasa, María Teresa ; Eizmendi Garate, Inmaculada; Elordi Güenaga, Udane; Elorza Puyadena, María Isabel; Huitzi Egilegor, Joseba Xabier ; Izagirre Otaegi, Andrea; Jiménez Marcos, María Anunciación; Lasa Labaca, Garbiñe; Liceaga Otazu, Nerea; Mayoz Echaniz, María Iciar; Pereda Goikoetxea, Beatriz; Tazón Ansola, María Pilar; Ugartemendia Yerobi, Maider; Zinkunegi Zubizarreta, Nagore; Zubeldia Etxeberria, Josune (2021-07-22)[ES]En este documento se presenta el diseño de la titulación de Grado en Enfermería de la UPV/EHU realizado en el marco de un proyecto de innovación, con metodología participativa y con la orientación durante todo el proceso ... -
Psychoeducational preventive treatment for women at risk of postpartum depression: study protocol for a randomized controlled trial, PROGEA
Ugarte Ugarte, Amaia; López-Peña, Purificación; Serrulla Vangeneberg, Carmen; Torregaray Royo, Julia Gemma; Arrieta Ugarte, Maria Asunción; Zabalza Compains, Maria Teresa; Riaño Medrano, Maria Pilar; Muñoz Toyos, Nerea; Arenaza Lamo, Edurne; Beneitez Dueñas, Maria Begoña; González Pinto Arrillaga, Ana María (Biomed Central, 2017-06-13)Background: Postpartum depression is a disease with a prevalence of 20% that has deleterious consequences not only for the mother but also for the baby and can cause delays in physical, social and cognitive development. ... -
Gene–Diet Interactions in Colorectal Cancer: Survey Design, Instruments, Participants and Descriptive Data of a Case–Control Study in the Basque Country
Alegría Lertxundi, Iker; Aguirre Gómez, Carmelo; Bujanda Fernández de Pierola, Luis ; Fernández Pablos, Francisco Javier; Polo, Francisco; Ordovás, José María; Etxezarraga Zuluaga, María Carmen; Zabalza Estévez, Ignacio; Larzabal, Mikel; Portillo Villares, María Isabel; Martínez de Pancorbo Gómez, María de los Angeles ; Palencia Madrid, Leire ; García Etxebarria, Koldo; Rocandio Pablo, Ana María ; Arroyo Izaga, Marta (MDPI, 2020)Epidemiologic studies have revealed inconsistent evidence of gene-diet interaction in relation to colorectal cancer (CRC). The aim of this study was to analyze them in a sample of cases and controls from the population-based ...