Liver governs adipose remodelling via extracellular vesicles in response to lipid overload
Liver governs adipose remodelling via extracellular vesicles in response to lipid overload
复制标题
肝脏通过细胞外囊泡响应脂质超载来控制脂肪重塑
DOI：
10.1038/s41467-020-14450-6
复制
发表时间：
2020-02-05
影响因子：
16.6
通讯作者：
Li, Chao-Jun
中科院分区：
文献类型：
--
作者：
Zhao, Yue;Zhao, Meng-Fei;Li, Chao-Jun
脂质过载导致脂质在代谢器官如肝脏、脂肪和肌肉之间重新分布;因此，肝脏和其他器官之间的相互作用对于维持脂质稳态很重要。在这里，我们发现肝脏首先对脂质过载做出反应，并发送肝细胞衍生的细胞外囊泡（EV）靶向脂肪细胞以调节脂肪生成和脂肪生成。肝脏中的香叶基香叶基二磷酸合酶（Ggpps）表达通过脂质过载增强，并通过Rab 27 A香叶基香叶基化调节EV分泌。一致地，肝脏特异性Ggps缺陷小鼠具有减少的脂肪沉积。非酒精性脂肪性肝病（NAFLD）患者血浆中几种EV衍生的miRNA水平与体重指数（BMI）正相关，并且这些miRNA增强脂肪细胞脂质积累。因此，我们强调了一个器官间机制，肝脏感知不同的代谢状态，并发送相应的信号来重塑脂肪组织，以适应脂质过载时的代谢变化。
Lipid overload results in lipid redistribution among metabolic organs such as liver, adipose, and muscle; therefore, the interplay between liver and other organs is important to maintain lipid homeostasis. Here, we show that liver responds to lipid overload first and sends hepatocyte-derived extracellular vesicles (EVs) targeting adipocytes to regulate adipogenesis and lipogenesis. Geranylgeranyl diphosphate synthase (Ggpps) expression in liver is enhanced by lipid overload and regulates EV secretion through Rab27A geranylgeranylation. Consistently, liver-specificGgppsdeficient mice have reduced fat adipose deposition. The levels of several EV-derived miRNAs in the plasma of non-alcoholic fatty liver disease (NAFLD) patients are positively correlated with body mass index (BMI), and these miRNAs enhance adipocyte lipid accumulation. Thus, we highlight an inter-organ mechanism whereby the liver senses different metabolic states and sends corresponding signals to remodel adipose tissue to adapt to metabolic changes in response to lipid overload.