Impaired Expression of the Inducible cAMP Early Repressor Accounts for Sustained Adipose CREB Activity in Obesity
| العنوان: | Impaired Expression of the Inducible cAMP Early Repressor Accounts for Sustained Adipose CREB Activity in Obesity |
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| المؤلفون: | Amar Abderrahmani, Chantal Verdumo, Vittorio Giusti, Bart Staels, Robert Caiazzo, Eric Le Gouill, Romano Regazzi, Gérard Waeber, Kim-Anne Lê, Peter Vollenweider, François Pattou, Dimitri Favre, Giulia Chinetti-Gbaguidi, Luc Tappy, Denis Fahmi |
| المصدر: | Diabetes Diabetes, vol. 60, no. 12, pp. 3169-3174 |
| بيانات النشر: | American Diabetes Association, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Male, endocrine system, medicine.medical_specialty, Adipose Tissue, White, Endocrinology, Diabetes and Metabolism, Glucose uptake, Blotting, Western, Activating transcription factor, Adipose tissue, Electrophoretic Mobility Shift Assay, 030209 endocrinology & metabolism, White adipose tissue, Intra-Abdominal Fat, Biology, Real-Time Polymerase Chain Reaction, CREB, 3T3-L1 Cells, Activating Transcription Factor 3/genetics, Activating Transcription Factor 3/metabolism, Adiponectin/genetics, Adiponectin/metabolism, Adipose Tissue, White/metabolism, Animals, 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, Glucose Transporter Type 4/genetics, Glucose Transporter Type 4/metabolism, Humans, Intra-Abdominal Fat/metabolism, Mice, Mice, Inbred C57BL, Obesity/genetics, Obesity/metabolism, Cyclic AMP Response Element Modulator, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Insulin resistance, Internal medicine, Adipocyte, Internal Medicine, medicine, Obesity, Cyclic AMP Response Element-Binding Protein, health care economics and organizations, 030304 developmental biology, 0303 health sciences, Activating Transcription Factor 3, Glucose Transporter Type 4, medicine.disease, humanities, Endocrinology, chemistry, biology.protein, Adiponectin, Obesity Studies, GLUT4 |
| الوصف: | OBJECTIVE Increase in adipose cAMP-responsive element\x{2013}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 METHODS 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. RESULTS 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. CONCLUSIONS Impaired expression of ICER contributes to elevation in CREB target genes and, therefore, to the development of insulin resistance in obesity. |
| وصف الملف: | application/pdf |
| تدمد: | 1939-327X 0012-1797 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fbcb52c52fc98ebfb9f5ab278961cbd3Test https://doi.org/10.2337/db10-1743Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....fbcb52c52fc98ebfb9f5ab278961cbd3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1939327X 00121797 |
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