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 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.
OBJECTIVE: Increase in adiposecAMP-responsive element binding protein (CREB) activity promotes adipocyte dysfunction and systemic insulin resistance in obesemice. 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 obesemice 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 obesehumans 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.
Authors: E D Abel; O Peroni; J K Kim; Y B Kim; O Boss; E Hadro; T Minnemann; G I Shulman; B B Kahn Journal: Nature Date: 2001-02-08 Impact factor: 49.962
Authors: Sarah R Preis; Joseph M Massaro; Sander J Robins; Udo Hoffmann; Ramachandran S Vasan; Thomas Irlbeck; James B Meigs; Patrice Sutherland; Ralph B D'Agostino; Christopher J O'Donnell; Caroline S Fox Journal: Obesity (Silver Spring) Date: 2010-03-25 Impact factor: 5.002
Authors: H Duplain; R Burcelin; C Sartori; S Cook; M Egli; M Lepori; P Vollenweider; T Pedrazzini; P Nicod; B Thorens; U Scherrer Journal: Circulation Date: 2001-07-17 Impact factor: 29.690
Authors: A Peri; B Conforti; S Baglioni-Peri; P Luciani; F Cioppi; L Buci; S Corbetta; E Ballaré; M Serio; A Spada Journal: J Clin Endocrinol Metab Date: 2001-05 Impact factor: 5.958