Loss of the RNA polymerase III repressor MAF1 confers obesity resistance.

Détails

Ressource 1Télécharger: 934.pdf (5651.52 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_F415BF94B601
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Loss of the RNA polymerase III repressor MAF1 confers obesity resistance.
Périodique
Genes and Development
Auteur(s)
Bonhoure N., Byrnes A., Moir R.D., Hodroj W., Preitner F., Praz V., Marcelin G., Chua S.C., Martinez-Lopez N., Singh R., Moullan N., Auwerx J., Willemin G., Shah H., Hartil K., Vaitheesvaran B., Kurland I., Hernandez N., Willis I.M.
ISSN
1549-5477 (Electronic)
ISSN-L
0890-9369
Statut éditorial
Publié
Date de publication
2015
Volume
29
Numéro
9
Pages
934-947
Langue
anglais
Résumé
MAF1 is a global repressor of RNA polymerase III transcription that regulates the expression of highly abundant noncoding RNAs in response to nutrient availability and cellular stress. Thus, MAF1 function is thought to be important for metabolic economy. Here we show that a whole-body knockout of Maf1 in mice confers resistance to diet-induced obesity and nonalcoholic fatty liver disease by reducing food intake and increasing metabolic inefficiency. Energy expenditure in Maf1(-/-) mice is increased by several mechanisms. Precursor tRNA synthesis was increased in multiple tissues without significant effects on mature tRNA levels, implying increased turnover in a futile tRNA cycle. Elevated futile cycling of hepatic lipids was also observed. Metabolite profiling of the liver and skeletal muscle revealed elevated levels of many amino acids and spermidine, which links the induction of autophagy in Maf1(-/-) mice with their extended life span. The increase in spermidine was accompanied by reduced levels of nicotinamide N-methyltransferase, which promotes polyamine synthesis, enables nicotinamide salvage to regenerate NAD(+), and is associated with obesity resistance. Consistent with this, NAD(+) levels were increased in muscle. The importance of MAF1 for metabolic economy reveals the potential for MAF1 modulators to protect against obesity and its harmful consequences.
Pubmed
Web of science
Open Access
Oui
Création de la notice
21/05/2015 9:19
Dernière modification de la notice
20/08/2019 17:21
Données d'usage