The nuclear orphan receptor COUP-TFII plays an essential role in adipogenesis, glucose homeostasis, and energy metabolism.

The nuclear orphan receptor COUP-TFII plays an essential role in adipogenesis, glucose homeostasis, and energy metabolism.
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DOI:
10.1016/j.cmet.2008.12.002
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发表时间:
2009-01-07
期刊:
影响因子:
29
通讯作者:
Tsai, Ming-Jer
Tsai, Ming-Jer
中科院分区:
生物学1区
文献类型:
--
作者:
Li, Luoping;Xie, Xin;Qin, Jun;Jeha, George S.;Saha, Pradip K.;Yan, Jun;Haueter, Claire M.;Chan, Lawrence;Tsai, Sophia Y.;Tsai, Ming-Jer

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脂肪组织的发育和功能在代谢综合征的发病机制和病理生理学中起着核心作用。在这里,我们表明,鸡卵清蛋白上游启动子转录因子II(COUP-TFII)在脂肪形成和能量稳态中起着关键作用。COUP-TFII在白色脂肪细胞(WAT)发育的早期阶段表达。COUP-TFII杂合子小鼠(COUP-TFII+/-)的WAT比野生型小鼠(COUP-TFII+/+)低得多。COUP-TFII+/-小鼠显示WAT发育的关键调节因子表达降低。在3 T3-L1细胞中敲低COUP-TFII导致Wnt 10 b表达增加,而染色质免疫沉淀分析显示Wnt 10 b是COUP-TFII的直接靶点。此外,COUP-TFII+/−小鼠增加了WAT中的线粒体生物合成,COUP-TFII+/−小鼠改善了葡萄糖稳态并增加了能量消耗。因此,COUP-TFII通过调节脂肪细胞发育中的关键分子来调节脂肪形成,并且可以作为调节能量代谢的新靶点。
Adipose tissue development and function play a central role in the pathogenesis and pathophysiology of metabolic syndromes. Here we show that Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) plays a pivotal role in adipogenesis and energy homeostasis. COUP-TFII is expressed in the early stages of white adipocyte (WAT) development. COUP-TFII heterozygous mice (COUP-TFII+/-) have much less WAT than wild type mice (COUP-TFII+/+). COUP-TFII+/- mice display a decreased expression of key regulators for WAT development. Knock down COUP-TFII in 3T3-L1 cells resulted in an increased expression of Wnt10b, while chromatin immunoprecipitation analysis revealed that Wnt10b is a direct target of COUP-TFII. Moreover, COUP-TFII+/− mice have increased mitochondrial biogenesis in WAT, and COUP-TFII+/− mice have improved glucose homeostasis and increased energy expenditure. Thus, COUP-TFII regulates adipogenesis by regulating the key molecules in adipocyte development, and can serve as a new target for regulating energy metabolism.
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