Titre :

Inhibition of ATG3 ameliorates liver steatosis by increasing mitochondrial function.

Auteur(s) :

Da Silva Lima, Natalia [Auteur]
Fondevila, Marcos F. [Auteur]
Nóvoa, Eva [Auteur]
Buqué, Xabier [Auteur]
Mercado-Gómez, Maria [Auteur]
Gallet, Sarah [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
González-Rellan, M. J. [Auteur]
Fernandez, Uxia [Auteur]
Loyens, Anne [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Garcia-Vence, Maria J. [Auteur]
Chantada-Vazquez, Maria del Pilar [Auteur]
Bravo, Susana B. [Auteur]
Marañon, Patricia [Auteur]
Senra, Ana [Auteur]
Escudero, Adriana [Auteur]
Leiva, Magdalena [Auteur]
Guallar, Diana [Auteur]
Fidalgo, Miguel [Auteur]
Gomes, Pedro [Auteur]
Claret, Marc [Auteur]
Sabio, Guadalupe [Auteur]
Varela-Rey, Marta [Auteur]
Delgado, Teresa C. [Auteur]
Montero-Vallejo, Rocio [Auteur]
Ampuero, Javier [Auteur]
López, Miguel [Auteur]
Diéguez, Carlos [Auteur]
Herrero, Laura [Auteur]
Serra, Dolors [Auteur]
Schwaninger, Markus [Auteur]
Prevot, Vincent [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Gallego-Duran, Rocio [Auteur]
Romero-Gomez, Manuel [Auteur]
Iruzubieta, Paula [Auteur]
Crespo, Javier [Auteur]
Martinez-Chantar, Maria L. [Auteur]
Garcia-Monzon, Carmelo [Auteur]
Gonzalez-Rodriguez, Agueda [Auteur]
Aspichueta, Patricia [Auteur]
Nogueiras, Ruben [Auteur]

Titre de la revue :

Journal of Hepatology

Nom court de la revue :

J Hepatol

Numéro :

76

Pagination :

11-24

Date de publication :

2021-09-20

ISSN :

1600-0641

Mot(s)-clé(s) en anglais :

ATG3
sirtuin 1
lipid metabolism
NAFLD
NASH
mitochondria

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [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 ...
Lire la suite >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 non-alcoholic 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 in humans and mice. Hepatic knockdown of ATG3 ameliorates the development of NAFLD by stimulating mitochondrial function. Thus, ATG3 is an important factor implicated in steatosis.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Date de dépôt :

2024-06-24T21:22:56Z
2024-11-28T13:13:32Z
2025-01-23T13:04:54Z