Faculty of Health Sciences, School of Medicine, Institute of Biomedicine, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland.
Faculty of Science, Forestry and Technology, Department of Technical Physics, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland.
J Transl Med. 2024 Jul 4;22(1):623. doi: 10.1186/s12967-024-05249-w.
Obesity is a worldwide epidemic characterized by adipose tissue (AT) inflammation. AT is also a source of extracellular vesicles (EVs) that have recently been implicated in disorders related to metabolic syndrome. However, our understanding of mechanistic aspect of obesity's impact on EV secretion from human AT remains limited.
We investigated EVs from human Simpson Golabi Behmel Syndrome (SGBS) adipocytes, and from AT as well as plasma of subjects undergoing bariatric surgery. SGBS cells were treated with TNFα, palmitic acid, and eicosapentaenoic acid. Various analyses, including nanoparticle tracking analysis, electron microscopy, high-resolution confocal microscopy, and gas chromatography-mass spectrometry, were utilized to study EVs. Plasma EVs were analyzed with imaging flow cytometry.
EVs from mature SGBS cells differed significantly in size and quantity compared to preadipocytes, disagreeing with previous findings in mouse adipocytes and indicating that adipogenesis promotes EV secretion in human adipocytes. Inflammatory stimuli also induced EV secretion, and altered EV fatty acid (FA) profiles more than those of cells, suggesting the role of EVs as rapid responders to metabolic shifts. Visceral AT (VAT) exhibited higher EV secretion compared to subcutaneous AT (SAT), with VAT EV counts positively correlating with plasma triacylglycerol (TAG) levels. Notably, the plasma EVs of subjects with obesity contained a higher number of adiponectin-positive EVs than those of lean subjects, further demonstrating higher AT EV secretion in obesity. Moreover, plasma EV counts of people with obesity positively correlated with body mass index and TNF expression in SAT, connecting increased EV secretion with AT expansion and inflammation. Finally, EVs from SGBS adipocytes and AT contained TAGs, and EV secretion increased despite signs of less active lipolytic pathways, indicating that AT EVs could be involved in the mobilization of excess lipids into circulation.
We are the first to provide detailed FA profiles of human AT EVs. We report that AT EV secretion increases in human obesity, implicating their role in TAG transport and association with adverse metabolic parameters, thereby emphasizing their role in metabolic disorders. These findings promote our understanding of the roles that EVs play in human AT biology and metabolic disorders.
肥胖是一种全球性的流行疾病，其特征是脂肪组织（AT）炎症。AT 也是细胞外囊泡（EVs）的来源，最近这些 EVs 与代谢综合征相关的疾病有关。然而，我们对肥胖对人类 AT 中 EV 分泌的影响的机制方面的理解仍然有限。
我们研究了来自人类 Simpson Golabi Behmel 综合征（SGBS）脂肪细胞的 EV，以及来自接受减肥手术的患者的 AT 和血浆中的 EV。用 TNFα、棕榈酸和二十碳五烯酸处理 SGBS 细胞。利用纳米颗粒跟踪分析、电子显微镜、高分辨率共聚焦显微镜和气相色谱-质谱联用等各种分析方法研究 EV。用成像流动细胞术分析血浆 EV。
与前脂肪细胞相比，成熟的 SGBS 细胞的 EV 在大小和数量上有显著差异，这与之前在小鼠脂肪细胞中的发现不一致，表明脂肪生成促进了人类脂肪细胞中 EV 的分泌。炎症刺激也诱导了 EV 的分泌，并改变了 EV 脂肪酸（FA）谱，比细胞中的变化更大，表明 EV 作为对代谢变化的快速反应者的作用。内脏脂肪组织（VAT）比皮下脂肪组织（SAT）表现出更高的 EV 分泌，VAT 的 EV 计数与血浆三酰甘油（TAG）水平呈正相关。值得注意的是，肥胖患者的血浆 EV 中含有更多的脂联素阳性 EV，这表明肥胖患者的 AT 中 EV 分泌更高。此外，肥胖患者的血浆 EV 计数与 SAT 中的体重指数和 TNF 表达呈正相关，将增加的 EV 分泌与 AT 扩张和炎症联系起来。最后，SGBS 脂肪细胞和 AT 中的 EV 含有 TAG，尽管脂解途径的活动迹象减少，但 EV 分泌仍增加，这表明 AT EV 可能参与将多余的脂质动员到循环中。
我们是第一个提供人类 AT EV 详细 FA 谱的人。我们报告说，AT EV 的分泌在人类肥胖中增加，暗示它们在 TAG 转运中的作用以及与不良代谢参数的关联，从而强调了它们在代谢紊乱中的作用。这些发现促进了我们对 EV 在人类 AT 生物学和代谢紊乱中的作用的理解。
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