共 36 条
Adipose tissue-specific inactivation of the retinoblastoma protein protects against diabesity because of increased energy expenditure
被引:89
作者:

Dali-Youcef, Nassim
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机构: Univ Strasbourg 1, CNRS, Inst Natl St & Rech Med, Inst Genet & Biol Mol & Cellulaire Strasbourg, F-67404 Illkirch Graffenstaden, France

Mataki, Chikage
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机构: Univ Strasbourg 1, CNRS, Inst Natl St & Rech Med, Inst Genet & Biol Mol & Cellulaire Strasbourg, F-67404 Illkirch Graffenstaden, France

Coste, Agnes
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机构: Univ Strasbourg 1, CNRS, Inst Natl St & Rech Med, Inst Genet & Biol Mol & Cellulaire Strasbourg, F-67404 Illkirch Graffenstaden, France

Messaddeq, Nadia
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机构: Univ Strasbourg 1, CNRS, Inst Natl St & Rech Med, Inst Genet & Biol Mol & Cellulaire Strasbourg, F-67404 Illkirch Graffenstaden, France

Giroud, Sylvain
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机构: Univ Strasbourg 1, CNRS, Inst Natl St & Rech Med, Inst Genet & Biol Mol & Cellulaire Strasbourg, F-67404 Illkirch Graffenstaden, France

Blanc, Stephane
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机构: Univ Strasbourg 1, CNRS, Inst Natl St & Rech Med, Inst Genet & Biol Mol & Cellulaire Strasbourg, F-67404 Illkirch Graffenstaden, France

Koehl, Christian
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机构: Univ Strasbourg 1, CNRS, Inst Natl St & Rech Med, Inst Genet & Biol Mol & Cellulaire Strasbourg, F-67404 Illkirch Graffenstaden, France

Champy, Marie-France
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机构: Univ Strasbourg 1, CNRS, Inst Natl St & Rech Med, Inst Genet & Biol Mol & Cellulaire Strasbourg, F-67404 Illkirch Graffenstaden, France

Chambon, Pierre
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机构: Univ Strasbourg 1, CNRS, Inst Natl St & Rech Med, Inst Genet & Biol Mol & Cellulaire Strasbourg, F-67404 Illkirch Graffenstaden, France

Fajas, Lluis
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机构: Univ Strasbourg 1, CNRS, Inst Natl St & Rech Med, Inst Genet & Biol Mol & Cellulaire Strasbourg, F-67404 Illkirch Graffenstaden, France

Metzger, Daniel
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机构: Univ Strasbourg 1, CNRS, Inst Natl St & Rech Med, Inst Genet & Biol Mol & Cellulaire Strasbourg, F-67404 Illkirch Graffenstaden, France

Schoonjans, Kristina
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机构: Univ Strasbourg 1, CNRS, Inst Natl St & Rech Med, Inst Genet & Biol Mol & Cellulaire Strasbourg, F-67404 Illkirch Graffenstaden, France

Auwerx, Johan
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机构: Univ Strasbourg 1, CNRS, Inst Natl St & Rech Med, Inst Genet & Biol Mol & Cellulaire Strasbourg, F-67404 Illkirch Graffenstaden, France
机构:
[1] Univ Strasbourg 1, CNRS, Inst Natl St & Rech Med, Inst Genet & Biol Mol & Cellulaire Strasbourg, F-67404 Illkirch Graffenstaden, France
[2] Hop Univ Strasbourg, Lab Biochim Gen & Specialisee, F-67098 Strasbourg, France
[3] CNRS, UMR 7178, Dept Ecol Physiol & Ethol, Inst Pluridisciplinaire Hubert Curien, F-67087 Strasbourg 02, France
[4] Univ Strasbourg, F-67087 Strasbourg 02, France
[5] Inst Clin Souris, F-67404 Illkirch Graffenstaden, France
[6] Ctr Reg Lutte Contre Canc Val Aurelle, Metab & Canc Lab, F-34298 Montpellier 05, France
来源:
关键词:
brown adipose tissue;
mitochondria;
pocket proteins;
obesity;
D O I:
10.1073/pnas.0611568104
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 role of the tumor suppressor retinoblastoma protein (pRb) has been firmly established in the control of cell cycle, apoptosis, and differentiation. Recently, it was demonstrated that lack of pRb promotes a switch from white to brown adipocyte differentiation in vitro. We used the Cre-Lox system to specifically inactivate pRb in adult adipose tissue. Under a high-fat diet, pRb-deficient (pRb(ad-/-)) mice failed to gain weight because of increased energy expenditure. This protection against weight gain was caused by the activation of mitochondrial activity in white and brown fat as evidenced by histologic, electron microscopic, and gene expression studies. Moreover, pRb(-/-) mouse embryonic fibroblasts displayed higher proliferation and apoptosis rates than pRb(+/+) mouse embryonic fibroblasts, which could contribute to the altered white adipose tissue morphology. Taken together, our data support a direct role of pRb in adipocyte cell fate determination in vivo and suggest that pRb could serve as a potential therapeutic target to trigger mitochondrial activation in white adipose tissue and brown adipose tissue, favoring an increase in energy expenditure and subsequent weight loss.
引用
收藏
页码:10703 / 10708
页数:6
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机构: Univ London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London W12 0NN, England

Parker, MG
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机构: Univ London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London W12 0NN, England