Promyelocytic leukemia inhibits adipogenesis, and loss of promyelocytic leukemia results in fat accumulation in mice.

摘要: The function of the tumor suppressor promyelocytic leukemia (PML) protein is disrupted in leukemia. PML has been reported to as a negative regulator mTOR (mammalian target rapamycin) and nuclear Akt under some conditions. pathways regulate diverse array pathways, including those that control insulin signaling, energy metabolism, growth, cellular survival, lifespan. Although PML-mTOR/Akt link suggests may have metabolic functions whole organism, very little known about PML. Here we report PML−/− mice did not show any significant defects. There was no impairment mTOR/Akt or AMPK signaling white adipose tissue, liver, muscle. However, despite having normal food intake activity levels, gained body weight faster had more fat mass, particularly subcutaneous diet-induced obesity model. Using vitro adipogenesis models, discovered adipogenesis. expression decreased during undetectable fully differentiated adipocytes. Loss increased adipogenic transcription factors CCAAT/enhancer binding protein-α peroxisome proliferator-activated receptor-γ. We found Sirt1-NCor-SMRT corepressor complex, which represses pparg transcription, does bind promoter efficiently upon depletion. On basis these findings, propose that, times excess, limit accumulation by suppressing differentiation preadipocytes into