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营养感应的核受体协调自性自
Jae Man Lee1, Martin Wagner1, Rui Xiao1
1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Nature
|November 11, 2014
概括
营养受体PPARα和FXR控制肝脏自. 在养状态下,PPARα促进了自,而在禁食状态下,FXR抑制了它,揭示了关键的转录调节机制.
科学领域:
- 细胞生物学 细胞生物学
- 代谢过程中的代谢.
- 分子内分泌学分子内分泌学
背景情况:
- 自是一种营养回收和能量恒温的保存过程.
- 虽然对自的急性调节有所了解,但其长期的转录控制仍然不清楚.
- 核受体PPARα (禁食肝脏) 和FXR (食肝脏) 是关键的营养传感器.
研究的目的:
- 研究PPARα和FXR在小鼠肝脏自的转录调节中的作用.
- 阐明这些核受体是如何调节自的,以响应营养状况 (禁食与食).
主要方法:
- 在野生型小鼠中利用了PPARα和FXR的药理活性.
- 使用淘汰赛小鼠模型 (Ppara(-/-) 和Fxr(-/-)) 来评估功能角色.
- 通过检查与自相关的促进体结合和基因表达来分析转录调节.
主要成果:
- PPARα激活逆转了被养状态的自抑制,诱导了脂,这种反应在Ppara(-/-) 小鼠中不存在.
- FXR激活抑制了禁食状态的自诱导,在Fxr(-/-) 小鼠中没有这种反应.
- 发现PPARα和FXR在与共享的自基因促进体结合方面竞争,产生相反的转录效应.
结论:
- PPARα和FXR是肝脏自的关键调节者,对营养的可用性做出反应.
- 这些受体提供互补,相互锁定的转录机制,以控制基于营养状况的自.
- 这些发现揭示了对自的长期调节的新见解,超出了急性信号通路.
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