Leptin-induced transactivation of NPY gene promoter mediated by JAK1, JAK2 and STAT3 in the neural cell lines

Abstract

Neuropeptide Y (NPY) plays an important role in the central and sympathetic regulation of food intake and blood pressure. Although the NPY gene expression is regulated by a number of agents such as leptin, the mechanism responsible for leptin-induced regulation of the transcription of the NPY gene remains to be explored. In this study, the NPY gene promoter was transactivated by leptin in N18TG2, NG108-15 and PC12 cells which expressed the functional leptin receptor. The long isoform of leptin receptor (OB-Rb) could induce the transactivation, but the C-terminal truncated form (OB-Ra) could not. When dominant negative type of STAT3, JAK1 or JAK2 and was co-expressed, the leptin-induced transactivation was suppressed almost completely. The leptin-response element which confers NPY gene transactivation by leptin was determined in the 221-bp region of rat NPY gene promoter (−553/−335), where two STAT3-binding site-like elements (TCCAGTA) exist. These results indicated that activation of JAK1, JAK2 and STAT3 is necessary for leptin-induced transactivation of NPY gene through the leptin-response element in these neural cells.