Titre du document / Document title

SIRT1 regulates adiponectin gene expression through foxol-C/enhancer-binding protein a transcriptional complex

Auteur(s) / Author(s)

LIPING QIAO ; JIANHUA SHAO ;

Résumé / Abstract

Adiponectin is an adipose-derived hormone that plays an important role in maintaining energy homeostasis. Adiponectin gene expression is diminished in both obesity and type 2 diabetes. However, the mechanism underlying the impaired adiponectin gene expression remains poorly understood. Recent studies have indicated that forkhead transcription factor 01 (Foxol) and silent information regulator 2 mammalian ortholog SIRT1 are involved in adipogenesis. Here we have shown that Foxol up-regulates adiponectin gene transcription through a Foxol-responsive region in the mouse adiponectin promoter that contains two adjacent Foxol binding sites. Foxol interacts with CCAAT/enhancer-binding protein a (C/EBPa) to form a transcription complex at the mouse adiponectin promoter and up-regulates adiponectin gene transcription. Our study has revealed that C/EBPa accesses the adiponectin promoter through two Foxol binding sites and acts as a co-activator. Further, SIRT1 increases adiponectin transcription in adipocytes by activating Foxol and enhancing Foxol and C/EBPa interaction. Importantly, both Foxol and SIRT1 protein levels were significantly lower in epididymal fat tissues from db/db and high fat diet-induced obese mice compared with normal mice. We propose that low expression of SIRT1 and Foxol leads to impaired Foxol-C/EBPa complex formation, which contributes to the diminished adiponectin expression in obesity and type 2 diabetes.

Revue / Journal Title

The Journal of biological chemistry   ISSN 0021-9258   CODEN JBCHA3 

Source / Source

2006, vol. 281, n^o52, pp. 39915-39924 [10 page(s) (article)]

Langue / Language

Anglais

Editeur / Publisher

American Society for Biochemistry and Molecular Biology, Bethesda, MD, ETATS-UNIS  (1905) (Revue)

Localisation / Location

INIST-CNRS, Cote INIST : 3082, 35400014521315.0190