CCAAT/Enhancer Binding Protein and Nuclear Factor-Y Regulate Adiponectin Gene Expression in Adipose Tissue

Abstract

Adiponectin is one of the adipokines secreted by adipocytes and regulates energy homeostasis associated with insulin sensitivity, suggesting a possibility of nutritional regulation of adiponectin gene expression. In this study, we showed that the transcription of adiponectin gene was induced 4-6 h after refeeding of mice. Also, differentiated 3T3-L1 adipocytes that were treated with high glucose expressed significantly increased adiponectin mRNA. Promoter analysis using nuclear extracts from white adipose tissue revealed that CCAAT/enhancer binding protein (C/EBP) and nuclear factor-Y (NF-Y) bound on the -117/-73 region of the adiponectin promoter. This region was critical for the activity of the adiponectin promoter as the deletion or mutation of this region markedly diminished the promoter activity to a basal level. Furthermore, the C/EBP binding increased in both refed animal and high glucose-treated 3T3-L1 adipocytes in an electrophoretic mobility shift assay, suggesting that C/EBP is responsible for the dietary response of the adiponectin gene expression. Chromatin immunoprecipitation studies demonstrated the binding of C/EBP and NF-Y in both mouse and differentiated 3T3-L1 adipocytes and also that C/EBP binding increased in response to high glucose. These findings demonstrated that C/EBP and NF-Y are critical for the regulation of the adiponectin expression in response to nutrients and in the course of adipocyte differentiation.