Deficiency in the Nuclear Factor E2-related Factor-2 Transcription Factor Results in Impaired Adipogenesis and Protects against Diet-induced Obesity

摘要: Nuclear factor E2-related 2 (Nrf2) is a cap-n-collar basic leucine zipper (CNC-bZIP) transcription that well established as master regulator of phase II detoxification and antioxidant gene expression strongly expressed in tissues involved xenobiotic metabolism including liver kidney. Nrf2 also abundantly adipose tissue; however, the exact function adipocyte biology unclear. In current study we show targeted knock-out mice decreases tissue mass, promotes formation small adipocytes, protects against weight gain obesity otherwise induced by high fat diet. mouse embryonic fibroblasts, 3T3-L1 cells, human subcutaneous preadipocytes, selective deficiency impairs differentiation. Deficiency leads to decreased peroxisome proliferator-activated receptor γ (PPARγ), CCAAT enhancer-binding protein α (C/EBPα), their downstream targets during Conversely, activation cells stable knockdown its negative Keap1 enhances accelerates hormone-induced Transfection stimulates Pparγ promoter activity, PPARγ cells. addition, chromatin immunoprecipitation studies associates with consensus binding sites for promoter. These findings demonstrate novel biologic role beyond participation pathways place within limited network factors control differentiation regulating PPARγ.