Titre :

The Nutrient-Dependent O-GlcNAc Modification Controls the Expression of Liver Fatty Acid Synthase

Auteur(s) :

Baldini, Steffi F. [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Wavelet, Cindy [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Hainault, Isabelle [Auteur]
Centre de Recherche des Cordeliers [CRC]
Guinez, Céline [Auteur]
Environnement périnatal et croissance - EA 4489 [EPS]
Lefebvre, Tony [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Titre de la revue :

Journal of Molecular Biology

Nom court de la revue :

J. Mol. Biol.

Numéro :

428

Pagination :

3295-3304

Date de publication :

2016-08-14

ISSN :

1089-8638

Mot(s)-clé(s) en anglais :

Cell Line
Obesity
Liver
Mice, Inbred C57BL
ob/ob mice
N-Acetylglucosaminyltransferases
Animals
Fatty Acid Synthases
O-GlcNAcylation
FAS
Mice
Protein Processing, Post-Translational
Lipogenesis
Food

Discipline(s) HAL :

Chimie/Chimie théorique et/ou physique

Résumé en anglais : [en]

Liver Fatty Acid Synthase (FAS) is pivotal for de novo lipogenesis. Loss of control of this metabolic pathway contributes to the development of liver pathologies ranging from steatosis to nonalcoholic steatohepatitis (NASH) ...
Lire la suite >Liver Fatty Acid Synthase (FAS) is pivotal for de novo lipogenesis. Loss of control of this metabolic pathway contributes to the development of liver pathologies ranging from steatosis to nonalcoholic steatohepatitis (NASH) which can lead to cirrhosis and, less frequently, to hepatocellular carcinoma. Therefore, deciphering the molecular mechanisms governing the expression and function of key enzymes such as FAS is crucial. Herein, we link the availability of this lipogenic enzyme to the nutrient-dependent post-translational modification O-GlcNAc that is thought to be deregulated in metabolic diseases (diabetes, obesity, and metabolic syndrome). We demonstrate that expression and activity of liver FAS correlate with O-GlcNAcylation contents in ob/ob mice and in mice fed with a high-carbohydrate diet both in a transcription-dependent and -independent manner. More importantly, inhibiting the removal of O-GlcNAc residues in mice intraperitoneally injected with the selective and potent O-GlcNAcase (OGA) inhibitor Thiamet-G increases FAS expression. FAS and O-GlcNAc transferase (OGT) physically interact, and FAS is O-GlcNAc modified. Treatment of a liver cell line with drugs or nutrients that elevate the O-GlcNAcylation interferes with FAS expression. Inhibition of OGA increases the interaction between FAS and the deubiquitinase Ubiquitin-specific protease-2a (USP2A) in vivo and ex vivo, providing mechanistic insights into the control of FAS expression through O-GlcNAcylation. Together, these results reveal a new type of regulation of FAS, linked to O-GlcNAcylation status, and advance our knowledge on deregulation of lipogenesis in diverse forms of liver diseases.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

CNRS
Université de Lille

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Équipe(s) de recherche :

O-GlcNAcylation, signalisation cellulaire et cycle cellulaire

Date de dépôt :

2020-02-12T15:11:47Z
2021-07-13T07:51:39Z