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棕色脂肪组织的CoQ缺乏激活了综合应激反应和FGF21依赖的线粒激酶

Ching-Fang Chang¹, Amanda L Gunawan¹, Irene Liparulo¹

¹Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA, 94720, USA.

The EMBO journal

|January 11, 2024

概括

棕色脂肪中的辅酶Q (CoQ) 缺乏会激活压力反应,令人惊地提高新陈代谢并减少体重增加. 这一意想不到的发现突显了CoQQ.

科学领域:

线粒体生物学线粒体生物学
代谢调节代谢调节代谢调节
细胞应激反应的细胞应激反应

背景情况:

辅酶Q (CoQ) 对线粒体呼吸和棕色脂肪组织 (BAT) 热生成至关重要.
在BAT中缺乏CoQ的具体机制尚不清楚.

研究的目的:

在BAT中调查CoQ缺陷的机械后果.
探索CoQ缺乏对全身能量消耗和代谢适应的影响.

主要方法:

在BAT中对CoQ缺乏的药理和遗传诱导.
分析压力信号通路,包括综合应激反应 (ISR).
评估线粒体RNA积累,UCP1和FGF21表达的情况.
在高脂肪饮食中测量全身代谢率和体重变化.
研究BAT与 inguinal 白脂肪组织 (iWAT) 之间的组织间交叉.

主要成果:

在BAT中缺乏CoQ会触发细胞质线粒体RNA的积累,并激活PKR/eIF2α通路,从而启动ISR.
这导致抑制的UCP1,但诱导的FGF21表达.
尽管减少了UCP1,但BAT CoQ缺乏增加了全身代谢率,并减少了高脂肪饮食的体重增加.
特定于BAT的CoQ缺陷通过组织间交叉声促进iWAT色.

结论:

在BAT中缺乏CoQ会产生类似于线粒激素的效果,增加全身的能量消耗.
在ATF4-FGF21轴和BAT衍生FGF21中介这种代谢适应.
在调节能源消耗方面,CoQ起着至关重要的作用,对与CoQ相关的疾病有影响.

关键词:

棕色脂肪组织棕色脂肪组织辅酶Q 是一种辅酶Q.FGF21FGF21FGF21FGF21FGF21FGF21FGF21FGF21FGF21FGF21FGF21 线粒体展开的蛋白质反应线粒体的发生是线粒体的发生.

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