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- Title
Impaired expression of the inducible cAMP early repressor accounts for sustained adipose CREB activity in obesity.
- Authors
Favre D; Le Gouill E; Fahmi D; Verdumo C; Chinetti-Gbaguidi G; Staels B; Caiazzo R; Pattou F; Lê KA; Tappy L; Regazzi R; Giusti V; Vollenweider P; Waeber G; Abderrahmani A; Favre, Dimitri; Le Gouill, Eric; Fahmi, Denis; Verdumo, Chantal; Chinetti-Gbaguidi, Giulia
- Abstract
<bold>Objective: </bold>Increase in adipose cAMP-responsive element 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.<bold>Research Design and Methods: </bold>Total 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.<bold>Results: </bold>The 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.<bold>Conclusions: </bold>Impaired expression of ICER contributes to elevation in CREB target genes and, therefore, to the development of insulin resistance in obesity.
- Publication
Diabetes, 2011, Vol 60, Issue 12, p3169
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db10-1743