背景:肥胖是一种以脂肪组织(AT)炎症为特征的世界性流行病。AT也是最近与代谢综合征相关的疾病有关的细胞外囊泡(EV)的来源。然而,我们对肥胖对人类AT分泌EV影响的机制方面的理解仍然有限。
方法:我们研究了来自人类SimpsonGolabiBehmel综合征(SGBS)脂肪细胞的EV,来自AT以及接受减肥手术的受试者的血浆。SGBS细胞用TNFα处理,棕榈酸,和二十碳五烯酸.各种分析,包括纳米粒子跟踪分析,电子显微镜,高分辨率共聚焦显微镜,和气相色谱-质谱法,用于研究电动汽车。用成像流式细胞术分析血浆EV。
结果:与前脂肪细胞相比,来自成熟SGBS细胞的EV在大小和数量上存在显著差异,与先前在小鼠脂肪细胞中的发现不同,并表明脂肪生成促进人脂肪细胞中EV的分泌。炎症刺激也诱导EV分泌,和改变的EV脂肪酸(FA)分布比细胞更多,提示电动汽车作为代谢变化的快速反应者的作用。与皮下AT(SAT)相比,内脏AT(VAT)表现出更高的EV分泌,VATEV计数与血浆三酰甘油(TAG)水平呈正相关。值得注意的是,肥胖受试者的血浆EV比瘦受试者含有更多的脂联素阳性EV,进一步证明肥胖症中ATEV分泌较高。此外,肥胖人群的血浆EV计数与体重指数和SAT中TNF的表达呈正相关,将EV分泌增加与AT扩张和炎症联系起来。最后,来自SGBS脂肪细胞和AT的EV含有TAG,尽管有较不活跃的脂解途径的迹象,但EV分泌增加,表明ATEV可能参与将多余的脂质动员到循环中。
结论:我们率先提供了人类ATEV的详细FA谱。我们报告说,在人类肥胖中,ATEV分泌增加,暗示它们在TAG转运中的作用以及与不良代谢参数的关联,从而强调它们在代谢紊乱中的作用。这些发现促进了我们对电动汽车在人类AT生物学和代谢紊乱中的作用的理解。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.