INDUCTION OF BROWN ADIPOCYTES BY TRANSCRIPTION FACTOR NFE2L2

摘要

New methods have been developed to treat obesity or other human disorders by increasing the degree of brown adipose thermogenesis, by both increasing the growth and differentiation of brown adipose tissue and increasing its activity. A new use for the transcription factor NFE2l2 was developed to increase BAT thermogenesis by increasing the expression of Ucp1. For the first time, NFE2l2 was found to interact with the NF-E2 motif and to stimulate the expression of Ucp1 (Figure 9). By modulating the expression of the Nfe2l2 gene or the concentration of NFE2l2 protein, changes in brown adipose tissue thermogenesis can be achieved to treat various weight disorders. Additionally, the direct involvement of CREB binding to CRE2 to regulate Ucp1 expression was demonstrated. Furthermore, transient transfection assays of luciferase reporter constructs and site-directed mutagenesis indicated that CRE2 was involved in transcriptional regulation of the Ucp1 through interaction with a phosphorylated CREB. NFE2l2 can be combined with other known transcription factors, e.g., CREB, PGC1, RXR, RAR, and PPAR gamma, to increase BAT thermogenesis by increasing the expression of Ucp1.