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


ABSTRACT: 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.

SUBMITTER: Imai T 

PROVIDER: S-EPMC384783 | biostudies-literature | 2004 Mar

REPOSITORIES: biostudies-literature

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

Imai Takeshi T   Takakuwa Reiko R   Marchand Sandra S   Dentz Emilie E   Bornert Jean-Marc JM   Messaddeq Nadia N   Wendling Olivia O   Mark Manuel M   Desvergne Béatrice B   Wahli Walter W   Chambon Pierre P   Metzger Daniel D  

Proceedings of the National Academy of Sciences of the United States of America 20040316 13


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 tha  ...[more]

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