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

被引：314
作者：
Imai, T
Takakuwa, R
Marchand, S
Dentz, E
Bornert, JM
Messaddeq, N
Wendling, O
Mark, M
Desvergne, B
Wahli, W
Chambon, P
Metzger, D
机构：
[1] Univ Strasbourg 1, Inst Genet & Biol Mol & Cellulaire, CNRS, INSERM, F-67404 Illkirch Graffenstaden, France
[2] Inst Clin Souris, F-67404 Illkirch Graffenstaden, France
[3] Univ Lausanne, Natl Ctr Competence Res Frontiers Genom, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland
来源：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2004年 / 101卷 / 13期
关键词：
conditional somatic mutagenesis; tamoxifen-dependent; adipocyte maintenance; obesity; nuclear receptor;
D O I：
10.1073/pnas.0400356101
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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-ERT2 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.
引用
收藏
页码：4543 / 4547
页数：5
相关论文
共 17 条
[1]  
[Anonymous], 1999, The Adipose Organ
[2]   Peroxisome proliferator-activated receptors: Nuclear control of metabolism [J].
Desvergne, B ;
Wahli, W .
ENDOCRINE REVIEWS, 1999, 20 (05) :649-688
[3]   Understanding adipocyte differentiation [J].
Gregoire, FM ;
Smas, CM ;
Sul, HS .
PHYSIOLOGICAL REVIEWS, 1998, 78 (03) :783-809
[4]   Adipose-specific peroxisome proliferator-activated receptor γ knockout causes insulin resistance in fat and liver but not in muscle [J].
He, WM ;
Barak, Y ;
Hevener, A ;
Olson, P ;
Liao, D ;
Le, J ;
Nelson, M ;
Ong, E ;
Olefsky, JM ;
Evans, RM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (26) :15712-15717
[5]   Impaired adipogenesis and lipolysis in the mouse upon selective ablation of the retinoid X receptor α mediated by a tamoxifen-inducible chimeric Cre recombinase (Cre-ERT2) in adipocytes [J].
Imai, T ;
Jiang, M ;
Chambon, P ;
Metzger, D .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (01) :224-228
[6]   Insights into insulin resistance and type 2 diabetes from knockout mouse models [J].
Kadowaki, T .
JOURNAL OF CLINICAL INVESTIGATION, 2000, 106 (04) :459-465
[7]   Abnormal spermatogenesis in RXR beta mutant mice [J].
Kastner, P ;
Mark, M ;
Leid, M ;
Gansmuller, A ;
Chin, W ;
Grondona, JM ;
Decimo, D ;
Krezel, W ;
Dierich, A ;
Chambon, P .
GENES & DEVELOPMENT, 1996, 10 (01) :80-92
[8]   De novo adipogenesis in mice at the site of injection of basement membrane and basic fibroblast growth factor [J].
Kawaguchi, N ;
Toriyama, K ;
Nicodemou-Lena, E ;
Inou, K ;
Torii, S ;
Kitagawa, Y .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (03) :1062-1066
[9]   RXR gamma null mice are apparently normal and compound RXR alpha(+/-)/RXR beta(-/-)/RXR gamma(-/-) mutant mice are viable [J].
Krezel, W ;
Dupe, V ;
Mark, M ;
Dierich, A ;
Kastner, P ;
Chambon, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (17) :9010-9014
[10]   PPARγ mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance [J].
Kubota, N ;
Terauchi, Y ;
Miki, H ;
Tamemoto, H ;
Yamauchi, T ;
Komeda, K ;
Satoh, S ;
Nakano, R ;
Ishii, C ;
Sugiyama, T ;
Eto, K ;
Tsubamoto, Y ;
Okuno, A ;
Murakami, K ;
Sekihara, H ;
Hasegawa, G ;
Naito, M ;
Toyoshima, Y ;
Tanaka, S ;
Shiota, K ;
Kitamura, T ;
Fujita, T ;
Ezaki, O ;
Aizawa, S ;
Nagai, R ;
Tobe, K ;
Kimura, S ;
Kadowaki, T .
MOLECULAR CELL, 1999, 4 (04) :597-609
12