通过稳定PPARγ,YTHDC1促进产后棕色脂肪组织的发育和发热
Lihua Wang1, Yuqin Wang1,2, Kaixin Ding1
1HIT Center for Life Sciences, School of Life Science and Technology, State Key Laboratory of Matter Behaviors in Space Environment, Frontier Science Center for Interaction between Space Environment and Matter, Zhengzhou Research Institute, Harbin Institute of Technology, Harbin, 150001, China.
The EMBO journal
|May 12, 2025
概括
通过稳定PPARγ,m6A读者蛋白YTHDC1调节棕色脂肪的发育和能量代谢. 删除YTHDC1会损害棕色脂肪组织 (BAT) 功能和小鼠的能量消耗.
科学领域:
- 生物化学 生物化学
- 代谢过程中的代谢.
- 分子生物学分子生物学
背景情况:
- 棕色脂肪组织 (BAT) 对于不发的发热和能量平衡至关重要.
- 温度,老龄化和肥胖等因素影响着BAT活动.
- 关于 BAT 开发和热生成的精确分子调节因素仍然不完全理解.
研究的目的:
- 确定控制棕色脂肪组织 (BAT) 发育和热生成的新型分子机制.
- 研究m6A读者蛋白YTHDC1在规范BAT中的作用.
- 在能量代谢的背景下阐明YTHDC1和PPARγ之间的相互作用.
主要方法:
- 在BAT中使用了针对性删除Ythdc1的小鼠模型.
- 使用生物化学分析研究了YTHDC1,PPARγ和ARIH2之间的蛋白质-蛋白质相互作用.
- 评估了Ythdc1删除对PPARγ稳定性,BAT开发,热生成和能源支出的影响.
主要成果:
- 在小鼠中,YTHDC1充当了产后骨间BAT发育和能量代谢的关键调节者.
- YTHDC1通过其内在无序区域 (IDR) 直接与PPARγ结合,防止其被E3泛素结合酶ARIH2.2降解.
- 删除Ythdc1导致PPARγ降解的增加,导致BAT开发受损,热生成减少,能源支出受损.
结论:
- 通过稳定PPARγ,YTHDC1在维护BAT开发和功能方面发挥着关键作用.
- 这种调节机制独立于YTHDC1已知的m6A识别功能运行.
- 这些发现为能量恒温的分子控制和BAT生物学提供了新的见解.
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