棕色脂肪组织通过Syntaxin 4依赖性热灭菌途径的卷入
Xiaofan Yu1,2, Gabrielle Benitez1,2, Peter Tszki Wei3
1Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Nature communications
|April 2, 2024
概括
老龄化导致棕色脂肪组织 (BAT) 损失. 恢复合成素4 (STX4) 或抑制热灭可以防止这种下降,揭示了热原性功能障碍的关键机制.
科学领域:
- 代谢过程中的代谢.
- 细胞生物学 细胞生物学
- 衰老研究研究 衰老研究
背景情况:
- 棕色脂肪组织 (BAT) 卷积,以减少质量和功能为标志,随着衰老,高脂肪饮食或热中性住房发生.
- 这种卷入涉及增加的脂质液滴大小和特定的Ucp1-低棕色脂肪细胞群体,表现出热和减少的合成素4 (STX4).
研究的目的:
- 调查STX4和热病在衰老和发热功能障碍期间棕色脂肪组织卷积中的作用.
- 确定将STX4缺乏与BAT功能受损和热症联系起来的机制.
主要方法:
- 在老老鼠中单核RNA测序是BAT.
- 基因操纵 (Ucp1-STX4KO小鼠) 来研究STX4缺乏症.
- 评估BAT质量,热生成活性,热灭菌标记物和代谢途径 (氧化酸化,葡萄糖吸收,糖解).
主要成果:
- 陈旧的棕色脂肪细胞和Ucp1-STX4KO小鼠表现出减少的BAT质量,热能功能障碍和增加的热亡.
- 恢复STX4表达或抑制热致死改善了与年龄相关的BAT下降和功能障碍.
- 缺乏STX4会损害氧化酸化,葡萄糖吸收和糖解,导致ATP水平降低并触发热.
结论:
- 生理衰老和发热功能障碍是由棕色脂肪细胞中 pyroptotic 信号激活驱动的.
- STX4在保持BAT质量和功能的过程中起着至关重要的作用,其缺乏会通过热致死促进进化.
- 针对热或恢复STX4为与年龄相关的代谢衰退提供了潜在的治疗策略.
![Visualization and Quantification of Brown and Beige Adipose Tissues in Mice using [18F]FDG Micro-PET/MR Imaging](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F62460.jpg&w=3840&q=50)
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