State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University & Model Animal Research Center, Nanjing University, Nanjing, 210093, China.
MOE Key Laboratory of Model Animals for Disease Study, Department of Hepatobiliary Surgery & Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210093, China.
Nat Commun. 2020 Feb 5;11(1):719. doi: 10.1038/s41467-020-14450-6.
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-specific Ggpps deficient 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.
脂质过载会导致肝脏、脂肪和肌肉等代谢器官之间的脂质重新分布；因此，肝脏和其他器官之间的相互作用对于维持脂质平衡很重要。在这里，我们表明肝脏对脂质过载的反应是首先发生的，并向脂肪细胞发送肝细胞衍生的细胞外囊泡（EVs），以调节脂肪生成和脂生成。脂质过载会增强肝脏中的香叶基香叶基二磷酸合酶（Ggpps）表达，并通过 Rab27A 香叶基香叶基化调节 EV 分泌。一致地，肝脏特异性 Ggpps 缺陷小鼠的脂肪脂肪沉积减少。非酒精性脂肪性肝病（NAFLD）患者血浆中几种 EV 衍生的 miRNAs 的水平与体重指数（BMI）呈正相关，这些 miRNAs 增强脂肪细胞的脂质积累。因此，我们强调了一种器官间的机制，即肝脏感知不同的代谢状态，并向脂肪组织发送相应的信号，以重塑脂肪组织，以适应脂质过载引起的代谢变化。
