Prolyl Isomerase Pin1 Suppresses Thermogenic Programs in Adipocytes by Promoting Degradation of Transcriptional Co-activator PRDM16.
Prolyl Isomerase Pin1 Suppresses Thermogenic Programs in Adipocytes by Promoting Degradation of Transcriptional Co-activator PRDM16.
复制标题
DOI：
10.1016/j.celrep.2019.02.066
复制
发表时间：
2019-03
期刊：
影响因子：
8.8
通讯作者：
Yusuke Nakatsu;Y. Matsunaga;Takeshi Yamamotoya;K. Ueda;Masa-Ki Inoue;Yu Mizuno;M. Nakanishi;T. Sano;Yosuke Yamawaki;A. Kushiyama;H. Sakoda;M. Fujishiro;A. Ryo;Hiraku Ono;T. Minamino;Shin-ichiro Takahashi;H. Ohno;M. Yoneda;Kei Takahashi;H. Ishihara;H. Katagiri;F. Nishimura;T. Kanematsu;Tetsuya Yamada;T. Asano
中科院分区：
文献类型：
--
作者：
Yusuke Nakatsu;Y. Matsunaga;Takeshi Yamamotoya;K. Ueda;Masa-Ki Inoue;Yu Mizuno;M. Nakanishi;T. Sano;Yosuke Yamawaki;A. Kushiyama;H. Sakoda;M. Fujishiro;A. Ryo;Hiraku Ono;T. Minamino;Shin-ichiro Takahashi;H. Ohno;M. Yoneda;Kei Takahashi;H. Ishihara;H. Katagiri;F. Nishimura;T. Kanematsu;Tetsuya Yamada;T. Asano
脂肪细胞中的非颤抖性产热提供了对低温和肥胖发展的防御，但潜在的调节机制仍有待充分阐明。基于Pin 1基因敲除小鼠在营养过剩状态下Pin 1表达的显著增加和对肥胖发展的抵抗，我们推测脂肪细胞Pin 1可能在产热程序中发挥作用。脂肪特异性Pin 1基因敲除（adPin 1 KO）小鼠表现出增强的产热基因转录和低温耐受性暴露于寒冷。此外，adPin 1 KO小鼠对高脂饮食诱导的肥胖和葡萄糖耐受不良具有抗性。一系列的实验表明，Pin 1结合PRDM 16，从而促进其通过泛素-蛋白酶体系统的降解。与这些结果一致，在分化的脂肪细胞中Pin 1缺失显示通过PRDM 16蛋白的上调响应于β3激动剂CL 316243的产热程序增强。这些观察结果表明，Pin 1是非颤抖性产热的负调节因子。
Non-shivering thermogenesis in adipocytes provides defense against low temperatures and obesity development, but the underlying regulatory mechanism remains to be fully clarified. Based on both markedly increased Pin1 expression in states of excess nutrition and resistance to obesity development in Pin1 null mice, we speculated that adipocyte Pin1 may play a role in thermogenic programs. Adipose-specific Pin1 knockout (adPin1 KO) mice showed enhanced transcription of thermogenic genes and tolerance to hypothermia when exposed to cold. In addition, adPin1 KO mice were resistant to high-fat diet-induced obesity and glucose intolerance. A series of experiments revealed that Pin1 binds to PRDM16 and thereby promotes its degradation through the ubiquitin-proteasome system. Consistent with these results, Pin1 deletion in differentiated adipocytes showed enhancement of thermogenic programs in response to the β3 agonist CL316243 through the upregulation of PRDM16 proteins. These observations indicate that Pin1 is a negative regulator of non-shivering thermogenesis.