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 (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.
Imai
Takeshi
T
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Université Louis Pasteur, BP10142, 1 Rue Laurent Fries, 67404 Illkirch, France.
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
D017667:Adipocytes / Q000166:cytology* / Q000502:physiology; D000273:Adipose Tissue / Q000166:cytology* / Q000502:physiology; D002001:Adipose Tissue, Brown / Q000166:cytology* / Q000502:physiology; D000818:Animals; D001483:Base Sequence; D002470:Cell Survival; D017931:DNA Primers; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017384:Sequence Deletion; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D017931:DNA Primers; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors