内皮细胞FUNDC1通过SIRT3/GATA2/内皮蛋白-1轴调节新陈代谢重编程和肥胖-糖尿病过渡
Jian Li1, Dayong Li2, Fujie Zhao1
1Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.
Nature communications
|January 16, 2026
概括
内皮细胞中的线粒体蛋白FUNDC1驱动肥胖和2型糖尿病. 阻断FUNDC1通过调节血管应激和胰岛素耐药性,防止代谢障碍.
科学领域:
- 血管生物学 血管生物学
- 代谢疾病 代谢疾病
- 线粒体功能的功能
背景情况:
- 内皮细胞 (EC) 功能障碍是肥胖和2型糖尿病 (T2DM) 的核心原因.
- 将血管应激与代谢疾病联系在一起的机制尚未完全理解.
- 在营养压力下的EC中,线粒体蛋白FUNDC1的作用需要研究.
研究的目的:
- 在营养过载期间研究线粒体蛋白FUNDC1在内皮细胞 (ECs) 中的作用.
- 阐明FUNDC1影响代谢健康和血管功能的分子机制.
主要方法:
- 使用了EC特定的Fundc1淘汰赛小鼠,食高脂肪饮食 (HFD).
- 采用了人类静脉EC,初级EC和来自肥胖/T2DM患者的血管组织.
- 分析了蛋白质定位,基因表达和代谢参数.
主要成果:
- 在糖尿病患者中,内皮FUNDC1表达升高,在肥胖/T2DM患者中与血ET-1正相关.
- 在ECs中删除FUNDC1,保护小鼠免受HFD诱导的肥胖,胰岛素耐药性和代谢障碍.
- FUNDC1调解SIRT3-L的核出口到线粒体,消毒GATA2并增加内甲蛋白-1 (ET-1) 的产生.
结论:
- 内皮FUNDC1在血管系统和代谢器官之间的交叉交互中起到关键调节者的作用.
- 在从肥胖转变为糖尿病的过程中,FUNDC1发挥着关键作用.
- 向内皮细胞FUNDC1可能为肥胖和T2DM提供治疗策略.
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