Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Glucose transporter GLUT4 protein, codified by Slc2a4 gene plays a key role in glycemic homeostasis. Insulin resistance, as in obesity, has been associated to inflammatory state, in which decreased GLUT4 is a feature. Inflammatory NF-kappa B transcriptional factor has been proposed as a repressor of Slc2a4; although, the binding site(s) in Slc2a4 promoter and the direct repressor effect have never been reported yet. A motif-based sequence analysis of mouse Slc2a4 promoter revealed two putative kappa B sites located inside -83/-62 and -134/-113 bp. Eletrophoretic mobility assay showed that p50 and p65 NF-kappa B subunits bind to both putative kappa B sites. Chromatin immunoprecipitation assay using genomic DNA from adipocytes confirmed p50- and p65-binding to Slc2a4 promoter. Moreover, transfection experiments revealed that NF-kappa B binds to the -134/-113 bp region of the mouse Slc2a4 gene promoter, inhibiting the Slc2a4 gene transcription. The current findings demonstrate the existence of two kappa B sites in Slc2a4 gene promote, and that NF-kappa B has a direct repressor effect upon the Slc2a4 gene, providing an important link between insulin resistance and inflammation. (C) 2013 Elsevier Ireland Ltd. All rights reserved.370416718795Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [07/50554-1, 08/09194-4, 11/08570-5]