Vesicles Shed by Pathological Murine Adipocytes Spread Pathology: Characterization and Functional Role of Insulin Resistant/Hypertrophied Adiposomes
Vesicles Shed by Pathological Murine Adipocytes Spread Pathology: Characterization and Functional Role of Insulin Resistant/Hypertrophied Adiposomes
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DOI：
10.3390/ijms21062252
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发表时间：
2020-03-01
影响因子：
5.6
通讯作者：
Pardo, Maria
中科院分区：
文献类型：
--
作者：
Camino, Tamara;Lago-Baameiro, Nerea;Pardo, Maria
细胞外囊泡（EV）最近已成为细胞与细胞通讯的相关方式，其分析已成为评估细胞/组织起源状态的间接方法。然而，关于它们的性质和在代谢性疾病中的作用的知识仍然非常缺乏。我们已经建立了胰岛素抵抗（IR）和两种脂质（棕榈酸/油酸）肥大脂肪细胞模型，以分离EV，通过质谱进行蛋白质货物定性和定量全理论质谱（SWATH）分析。我们的研究结果表明，在病理性EV中肥胖和IR相关蛋白的比例很高;因此，我们提出了一组潜在的肥胖脂肪组织EV生物标志物。其中，脂质肥大囊泡的特征在于血浆铜蓝蛋白、mimecan和围脂蛋白1脂肪因子，而来自IR的那些囊泡的特征在于肥胖和IR相关的转化生长因子β诱导蛋白ig-h3（TFGBI）的显著存在。有趣的是，功能测定显示IR和肥大的脂肪细胞通过分泌的EV诱导健康脂肪细胞的分化/肥大和IR。最后，我们证明了脂质萎缩的脂肪细胞脱落EV通过刺激IL-6和TNF α表达促进巨噬细胞炎症。因此，我们得出结论，病理性脂肪细胞释放囊泡含有代表性的蛋白质货物的细胞的起源，能够诱导健康细胞的代谢改变，可能加剧疾病一旦建立。
Extracellular vesicles (EVs) have recently emerged as a relevant way of cell to cell communication, and its analysis has become an indirect approach to assess the cell/tissue of origin status. However, the knowledge about their nature and role on metabolic diseases is still very scarce. We have established an insulin resistant (IR) and two lipid (palmitic/oleic) hypertrophied adipocyte cell models to isolate EVs to perform a protein cargo qualitative and quantitative Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH) analysis by mass spectrometry. Our results show a high proportion of obesity and IR-related proteins in pathological EVs; thus, we propose a panel of potential obese adipose tissue EV-biomarkers. Among those, lipid hypertrophied vesicles are characterized by ceruloplasmin, mimecan, and perilipin 1 adipokines, and those from the IR by the striking presence of the adiposity and IR related transforming growth factor-beta-induced protein ig-h3 (TFGBI). Interestingly, functional assays show that IR and hypertrophied adipocytes induce differentiation/hypertrophy and IR in healthy adipocytes through secreted EVs. Finally, we demonstrate that lipid atrophied adipocytes shed EVs promote macrophage inflammation by stimulating IL-6 and TNF alpha expression. Thus, we conclude that pathological adipocytes release vesicles containing representative protein cargo of the cell of origin that are able to induce metabolic alterations on healthy cells probably exacerbating the disease once established.