核受体Rev-erbα控制着昼夜发热性可塑性
Zachary Gerhart-Hines1,2, Dan Feng1,2, Matthew J Emmett1,2
1Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Nature
|October 29, 2013
概括
核受体Rev-erbα (Nr1d1) 将每日体温节律与适应寒冷的能力联系在一起. 丢失Rev-erbα可以提高耐寒性,并破坏温度节奏.
科学领域:
- 时间生物学 时间生物学
- 代谢调节 代谢调节 代谢调节 代谢调节
- 哺乳动物生理学哺乳动物生理学
背景情况:
- 哺乳动物表现出每天的体温节奏和对寒冷的平静反应.
- 昼夜节律和寒冷适应之间的分子联系仍然不清楚.
研究的目的:
- 研究核受体Rev-erbα (Nr1d1) 在协调昼夜体温节律和热生成中的作用.
- 阐明Rev-erbα影响棕色脂肪组织 (BAT) 功能和耐寒性能的机制.
主要方法:
- 使用了Rev-erbα删除 (Rev-erbα-null) 和野生类型对照的小鼠模型.
- 在一天的不同时间 (Zeitgeber时间) 评估寒冷耐受性.
- 测量了BAT和体温节奏中的脱蛋白1 (Ucp1) 表达式.
主要成果:
- Rev-erbα表达与寒冷耐受性相反相关;05:00 (ZT22) 的低表达与 17:00 (ZT10) 的高表达相比,与更好的耐受性相关.
- Rev-erbα-null小鼠表现出明显改善的寒冷耐受性,特别是在17:00时.
- Rev-erbα在BAT中直接抑制Ucp1的表达,并且它的缺失导致Ucp1水平升高,即使在热中性.
- 对Rev-erbα的遗传损失取消了正常的体温和BAT活动节奏.
结论:
- Rev-erbα作为昼夜和发热途径之间的关键分子链接.
- Rev-erbα是BAT功能,Ucp1诱导和每日体温节律的关键调节者.
- Rev-erbα的抑制功能对于适应热生成以应对寒冷等环境挑战至关重要.
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