Hippo-YAP/TAZ信号坐标通过将瘦素表达与脂肪质量脱而出的脂肪可塑性和能量平衡
Sungwoo Choi1,2, Ju-Gyeong Kang2, Yen T H Tran2
1Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
Nature metabolism
|May 29, 2024
概括
转录协调器YAP和TAZ通过调节脂肪细胞可塑性和基因表达来控制脂肪质量和瘦素水平,维持代谢平衡. 这一发现为脂肪组织功能和能量平衡提供了新的见解.
科学领域:
- 代谢调节 代谢调节 代谢调节
- 细胞的可塑性 细胞的可塑性
- 基因转录 基因转录
背景情况:
- 脂肪组织作为能量储存器和内分泌器官起作用.
- 协调脂肪组织功能的机制尚未完全理解.
- YAP和TAZ是转录性核心调节剂,在细胞生长和器官大小方面发挥作用.
研究的目的:
- 研究YAP/TAZ信号在脂肪细胞中的作用.
- 了解YAP/TAZ如何调节脂肪质量和瘦素水平.
- 阐明链接脂肪细胞可塑性与代谢平衡的机制.
主要方法:
- 在脂肪细胞中删除Lats1和Lats2,以激活YAP/TAZ信号传递.
- 分析脂肪质量,脂肪细胞形态和循环中的瘦素水平.
- 使用ChIP-seq和记者测试对YAP/TAZ-TEAD与丁基因增强剂的结合进行了调查.
- 在禁食和再养期间评估YAP/TAZ活动.
主要成果:
- 在脂肪细胞中激活YAP/TAZ信号,通过将成熟的脂肪细胞转化为原始类细胞来减少脂肪质量.
- 这种激活有悖论地增加了循环中的瘦素水平,防止了与脂质变相关的代谢功能障碍.
- 通过与上游增强剂结合,YAP/TAZ-TEAD 直接调高了瘦素的表达.
- 在禁食和再养期间,YAP/TAZ活性对瘦素调节至关重要.
结论:
- 脂肪细胞 Hippo-YAP/TAZ 信号协调脂质储存和能量平衡.
- 这种信号通路调节脂肪细胞的可塑性和瘦素基因转录.
- 通过脂肪组织调节,YAP/TAZ作为维持新陈代谢平衡的纽带.
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