Peroxisome proliferator-activated receptor [gamma] is required in mature white and brown adipocytes for their survival in the mouse

The peroxisome proliferator-activated receptor [gamma] (PPAR[gamma]) mediates the activity of the insulin-sensitizing thiazolidinediones and plays an important role in adipocyte differentiation and fat accretion. The analysis of PPAR[gamma], functions in mature adipocytes is precluded by lethality of PPAR[[gamma].sup.-/-] fetuses and tetraploid-rescued pups. Therefore we have selectively ablated PPAR[gamma] in adipocytes of adult mice by using the tamoxifen-dependent Cre-E[R.sup.T2] recombination system. We show that mature PPAR[gamma]-null white and brown adipocytes die within a few days and are replaced by newly formed PPAR[gamma]-positive adipocytes, demonstrating that PPAR[gamma], is essential for the in vivo survival of mature adipocytes, in addition to its well established requirement for their differentiation. Our data suggest that potent PPAR[gamma] antagonists could be used to acutely reduce obesity. conditional somatic mutagenesis | tamoxifen-dependent | adipocyte maintenance | obesity | nuclear receptor