Impaired expression of the inducible cAMP early repressor accounts for sustained adipose CREB activity in obesity.
Diabetes
; 60(12): 3169-74, 2011 Dec.
Article
em En
| MEDLINE
| ID: mdl-21998402
ABSTRACT
OBJECTIVE:
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. RESEARCH DESIGN ANDMETHODS:
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico
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Modulador de Elemento de Resposta do AMP Cíclico
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Obesidade
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Diabetes
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Suíça