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

Takeshi Imai , Reiko Takakuwa , Sandra Marchand , Emilie Dentz , Jean-Marc Bornert , Nadia Messaddeq (1, 2) , Olivia Wendling (1, 2) , Manuel Mark (1, 2) , Béatrice Desvergne , Walter Wahli , Pierre Chambon (1, 2) , Daniel Metzger (1, 2)

1 IGBMC - Institut de génétique et biologie moléculaire et cellulaire
2 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire

The peroxisome proliferator-activated receptor gamma (PPARgamma) mediates the activity of the insulin-sensitizing thiazolidinediones and plays an important role in adipocyte differentiation and fat accretion. The analysis of PPARgamma functions in mature adipocytes is precluded by lethality of PPARgamma(-/-) fetuses and tetraploid-rescued pups. Therefore we have selectively ablated PPARgamma in adipocytes of adult mice by using the tamoxifen-dependent Cre-ER(T2) recombination system. We show that mature PPARgamma-null white and brown adipocytes die within a few days and are replaced by newly formed PPARgamma-positive adipocytes, demonstrating that PPARgamma 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 PPARgamma antagonists could be used to acutely reduce obesity.

Domaines: Génétique

Takeshi Imai, Reiko Takakuwa, Sandra Marchand, Emilie Dentz, Jean-Marc Bornert, et al.. Peroxisome proliferator-activated receptor gamma is required in mature white and brown adipocytes for their survival in the mouse. Proceedings of the National Academy of Sciences of the United States of America, 2004, 101 (13), pp.4543-4547. ⟨10.1073/pnas.0400356101⟩. ⟨hal-04133444⟩