Impaired expression of the inducible cAMP early repressor accounts for sustained adipose CREB activity in obesity.

Détails

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Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_27E8D43FE47B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Impaired expression of the inducible cAMP early repressor accounts for sustained adipose CREB activity in obesity.
Périodique
Diabetes
Auteur(s)
Favre D., Le Gouill E., Fahmi D., Verdumo C., Chinetti-Gbaguidi G., Staels B., Caiazzo R., Pattou F.,  K.A., Tappy L., Regazzi R., Giusti V., Vollenweider P., Waeber G., Abderrahmani A.
ISSN
1939-327X (Electronic)
ISSN-L
0012-1797
Statut éditorial
Publié
Date de publication
2011
Volume
60
Numéro
12
Pages
3169-3174
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
OBJECTIVEIncrease in adipose cAMP response binding protein (CREB) activity promotes adipocyte dysfunction and systemic insulin resistance in obese mice. This is achieved by increasing the expression of activating transcription factor 3 (ATF3). In this study we investigated whether impaired expression of the inducible cAMP early repressor (ICER), a transcriptional antagonist of CREB, is responsible for the increased CREB activity in adipocytes of obese mice and humans.RESEARCH DESIGN AND METHODSTotal RNA and nuclear proteins were prepared from visceral adipose tissue (VAT) of human nonobese or obese subjects, and white adipose tissue (WAT) of C57Bl6-Rj mice that were fed with normal or high-fat diet for 16 weeks. The expression of genes was monitored by real-time PCR, Western blotting, and electromobility shift assays. RNA interference was used to silence the expression of Icer.RESULTSThe expression of Icer/ICER was reduced in VAT and WAT of obese humans and mice, respectively. Diminution of Icer/ICER was restricted to adipocytes and was accompanied by a rise of Atf3/ATF3 and diminution of Adipoq/ADIPOQ and Glut4/GLUT4. Silencing the expression of Icer in 3T3-L1 adipocytes mimicked the results observed in human and mice cells and hampered glucose uptake, thus confirming the requirement of Icer for appropriate adipocyte function.CONCLUSIONSImpaired expression of ICER contributes to elevation in CREB target genes and, therefore, to the development of insulin resistance in obesity.
Mots-clé
3T3-L1 Cells, Activating Transcription Factor 3/genetics, Activating Transcription Factor 3/metabolism, Adiponectin/genetics, Adiponectin/metabolism, Adipose Tissue, White/metabolism, Animals, Blotting, Western, Cyclic AMP Response Element Modulator/genetics, Cyclic AMP Response Element Modulator/metabolism, Cyclic AMP Response Element-Binding Protein/genetics, Cyclic AMP Response Element-Binding Protein/metabolism, Electrophoretic Mobility Shift Assay, Glucose Transporter Type 4/genetics, Glucose Transporter Type 4/metabolism, Humans, Intra-Abdominal Fat/metabolism, Male, Mice, Mice, Inbred C57BL, Obesity/genetics, Obesity/metabolism, Real-Time Polymerase Chain Reaction
Pubmed
Web of science
Open Access
Oui
Création de la notice
26/10/2011 12:30
Dernière modification de la notice
08/05/2019 16:05
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