转录协激活剂PGC-1alpha整合了哺乳动物的时钟和能量代谢
Chang Liu1, Siming Li, Tiecheng Liu
1Life Sciences Institute and Department of Cell & Developmental Biology, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA.
Nature
|May 4, 2007
概括
过氧体增殖器激活受体马协活性剂1-α (PGC-1alpha) 对于调节哺乳动物的昼夜钟和能量代谢至关重要. 它在肝脏和肌肉中的节奏表达整合了这些重要的生理过程.
科学领域:
- 分子生物学分子生物学
- 时间生物学 时间生物学
- 代谢过程中的代谢.
背景情况:
- 哺乳动物的昼夜时钟控制能量代谢,包括葡萄糖,脂质和线粒体功能.
- 连接昼夜节律和代谢途径的分子机制尚未完全理解.
研究的目的:
- 研究PGC-1alpha (Ppargc1a) 在能量代谢的昼夜调节中的作用.
- 为了阐明PGC-1alpha和核心时钟基因表达之间的关系.
主要方法:
- 在小鼠肝脏和骨肌中分析PGC-1alpha的节奏表达.
- 通过ROR核受体研究PGC-1alpha对钟基因表达 (Bmal1,Rev-erbalpha) 的影响.
- 对PGC-1alpha淘汰赛小鼠和肝脏特异性淘汰赛模型的表型分析.
- 在缺乏PGC-1α的纤维细胞中评估细胞自主时钟功能.
主要成果:
- PGC-1alpha在小鼠肝脏和骨肌中表现出节奏表达.
- PGC-1alpha通过与ROR核受体相互作用,共同激活钟基因Bmal1和Rev-erbalpha.
- 缺乏PGC-1α的小鼠表现出活动,体温和新陈代谢率中被破坏的白天节律.
- 在PGC-1α缺乏的小鼠中观察到异常的时钟基因表达和代谢基因失调.
- PGC-1alpha对于细胞自主生理时钟功能至关重要.
结论:
- PGC-1alpha被确定为一个关键的调节器,整合了哺乳动物的昼夜钟和能量代谢.
- 节奏性PGC-1α表达对于维持生理节奏和代谢平衡至关重要.
- 这项研究揭示了昼夜生物学和代谢控制之间的关键分子联系.
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