暴露于寒冷会通过ERRα和ERRγ诱导构成性活跃的热生成受体GPR3,通过ERRα和ERRγ
Olivia Sveidahl Johansen1, Rebecca L McIntyre2, Janane F Rahbani3
1Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
Molecular metabolism
|October 31, 2025
概括
与雌激素相关的受体α和gamma (ERRα/γ) 是冷暴露期间热生成脂肪细胞中Gpr3基因表达的关键调节者. 这一发现提供了一个可针对性的策略,以增加能源支出来打击肥胖.
科学领域:
- 代谢研究的研究.
- 脂肪细胞生物学 脂肪细胞生物学
- 基因调节 基因调节
背景情况:
- 增加能源消耗对于肥胖药物治疗至关重要.
- 热生成脂肪细胞,特别是棕色脂肪组织 (BAT),是能源消耗的关键目标.
- G蛋白结合受体3 (GPR3) 促进脂肪细胞的能量消耗,但其生理调节是未知的.
研究的目的:
- 为了确定调节Gpr3表达反应于冷暴露的因素.
- 研究雌激素相关受体 (ERR) 在冷诱导的Gpr3.3转录中的作用.
主要方法:
- ATAC-Seq被用来识别Gpr3.3的冷诱导促进元件.
- 针对ERRs生成了特定于脂肪的双重淘汰小鼠.
- 通过腺相关病毒 (AAV) 介导的救援实验在体内进行.
主要成果:
- ERRα直接与Gpr3.3的冷诱导促销元件结合.
- 在与PGC-1α共传染时,ERRα,ERRβ和ERRγ在体外激活Gpr3促进体.
- 脂肪细胞特异性ERRα和ERRγ对于冷暴露期间Gpr3转录诱导至关重要.
- 在AAV介导的ERRα或ERRγ在棕色脂肪组织中的再表达完全挽救了Gpr3冷诱导能力.
结论:
- ERRα和ERRγ是冷诱导Gpr3转录的关键调节者.
- 针对ERRα和ERRγ提出了一种药理上增强GPR3介导的能源消耗的策略.
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