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mTORC1控制着禁食诱导的生成及其因衰老而发生的调节
Shomit Sengupta1, Timothy R Peterson, Mathieu Laplante
1Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA.
Nature
|December 24, 2010
概括
拉巴胺素复合体1 (mTORC1) 的机械标通过调节PPARα.通过调节PPARα.控制着快餐期间肝脏生成. 抑制mTORC1可以恢复子的产生,即使在老年肝脏中,揭示了它在肝脏衰老中的作用.
科学领域:
- 细胞生物学 细胞生物学
- 代谢调节 代谢调节 代谢调节
- 身体生理学 身体生理学
背景情况:
- 拉巴胺素复合体1 (mTORC1) 途径的机械性标调节了基于营养素可用性的细胞生长.
- 虽然mTORC1的细胞功能是已知的,但它在肝脏生理学中的活体作用,特别是在禁食期间,理解程度较低.
- 肝脏在维持平衡中的作用包括在禁食期间产生体以获得能量.
研究的目的:
- 为了研究mTORC1在调节肝脏生成中的作用,以应对禁食.
- 阐明mTORC1影响体生产的分子机制.
- 探索mTORC1信号传递,衰老和肝功能之间的联系.
主要方法:
- 使用了对mTORC1组件 (TSC1,猛禽) 进行肝脏特异性基因操纵的小鼠模型.
- 评估肝脏大小,体生产,以及快食和食状态下的基因表达.
- 研究了mTORC1,PPARα和NCoR1在调节生成中的相互作用.
- 在老年小鼠中检查了mTORC1信号和生成.
主要成果:
- 失去了TSC1 (mTORC1抑制剂) 导致了耐快食肝脏生长和代功能受损.
- 捕食者 (mTORC1成分) 的损失产生了相反的效果,增强了生成.
- mTORC1抑制对于禁食诱导的PPARα激活和基因基因表达至关重要.
- 在过度活跃的mTORC1条件下抑制NCoR1重新激活的生成.
- 年龄较大的肝脏显示代功能受损,与增加的mTORC1信号相关.
- 抑制mTORC1可以防止与年龄相关的代缺陷.
结论:
- mTORC1是肝脏生成和PPARα活动的关键调节者.
- mTORC1信号在与年龄相关的肝功能下降中发挥着重要作用.
- 向mTORC1可能为衰老肝脏的代谢功能障碍提供治疗策略.
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