부산대학교 도서관

BACKGROUND:: We have previously reported an association between the activator protein-2β (AP-2β) transcription factor gene and type 2 diabetes. This gene is preferentially expressed in adipose tissue, and subjects with a disease-susceptible allele of AP-2β showed stronger AP-2β expression in adipose tissue than those without the susceptible allele. Furthermore, overexpression of AP-2β led to lipid accumulation and induced insulin resistance in 3T3-L1 adipocytes. RESULT:: We found that overexpression of AP-2β in 3T3-L1 adipocytes decreased the promoter activity of leptin, and subsequently decreased both messenger RNA (mRNA) and protein expression and secretion. Furthermore, knockdown of endogenous AP-2β by RNA-interference increased mRNA and protein expression of leptin. Electrophoretic mobility shift and chromatin immunoprecipitation assays revealed specific binding of AP-2β to leptin promoter regions in vitro and in vivo. In addition, site-directed mutagenesis of the AP-2-binding site located between position + 34 and + 42 relative to the transcription start site abolished the inhibitory effect of AP-2β. Our results clearly showed that AP-2β directly inhibited insulin-sensitizing hormone leptin expression by binding to its promoter. CONCLUSION:: AP-2β modulated the expression of leptin through direct interaction with its promoter region.