定义肝脏循环时钟的独立性
Kevin B Koronowski1, Kenichiro Kinouchi1, Patrick-Simon Welz2
1Center for Epigenetics and Metabolism, U1233 INSERM, Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA.
哺乳动物有自己的内在时钟来调节日常功能. 这项研究表明肝脏时钟具有一定自主性, 但仍需要来自其他时钟的信号和光线才能充分发挥作用.
科学领域:
- 时间生物学
- 分子生物学
- 代谢调节
背景情况:
- 哺乳动物拥有控制生理的生理时钟的等级网络.
- 超神核 (SCN) 作为中央节拍器,但外围时钟的自主性仍然不清楚.
- BMAL1是生物节律的关键蛋白质.
研究的目的:
- 在体内检测肝脏生理时钟的组织自主性.
- 确定肝脏时钟在多大程度上可以独立于心脏起器.
- 阐明BMAL1在肝脏特定的昼夜调节中的作用.
主要方法:
- 仅在肝脏中生成复制BMAL1表达的不律性Bmal1-零小鼠 (肝脏-RE).
- 高通量转录组和代谢组分析肝功能.
- 染色体占用分析以评估BMAL1结合点.
主要成果:
- 肝脏在代谢过程中表现出独立的昼夜功能,如NAD+救援和糖原周转.
- 尽管BMAL1与许多基因组位点结合,但只有~10%的转录在肝脏RE小鼠中显示昼夜表达.
- 在恒定的黑暗下,肝脏RE小鼠的节律时钟基因表达被废除.
结论:
- 肝脏的生理时钟具有一定程度的自主性,但并非完全独立.
- 肝脏的循环功能依赖于其他时钟和光线的外部信号.
- 在肝脏中,光线有助于组织自主时钟功能.
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