Human Adipocyte Extracellular Vesicles in Reciprocal Signaling Between Adipocytes and Macrophages
Human Adipocyte Extracellular Vesicles in Reciprocal Signaling Between Adipocytes and Macrophages
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DOI：
10.1002/oby.20679
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发表时间：
2014-05-01
期刊：
影响因子：
6.9
通讯作者：
Kalkhoven, Eric
中科院分区：
文献类型：
--
作者：
Kranendonk, Mariette E. G.;Visseren, Frank L. J.;Kalkhoven, Eric
目的：确定人脂肪细胞或脂肪组织（AT）外植体释放的细胞外囊泡（EVs）在脂肪细胞与巨噬细胞旁分泌相互作用中发挥作用，这是AT炎症导致胰岛素抵抗（IR）等代谢并发症的关键机制。方法：采用电镜、Western blot、多重脂肪因子分析和流式细胞术对体外分化脂肪细胞和at外植体释放的EVs进行表征。用来自脂肪细胞、皮下细胞（SCAT）或网膜源性细胞（OAT）的ev刺激原代单核细胞，并进行表型分析。随后使用巨噬细胞上清评估对脂肪细胞胰岛素信号传导的影响。结果：脂肪细胞和at来源的EVs将单核细胞分化为巨噬细胞，这是人类脂肪组织巨噬细胞（ATM）的特征，通过释放促炎性和抗炎细胞因子来定义。脂联素阳性的at衍生ev亚群，可能代表脂肪细胞衍生ev，诱导比脂联素阴性的at - ev更明显的atm表型。这种效应在oat - ev和scat - ev中更为明显。此外，at - ev预刺激巨噬细胞上清可干扰人脂肪细胞的胰岛素信号传导。最后，oat衍生的ev数量与患者HOMA-IR呈正相关。结论：人类at - ev可能在脂肪细胞和巨噬细胞之间的相互促炎循环中发挥作用，并有可能加重局部和全身IR。
Objective: Extracellular vesicles (EVs) released by human adipocytes or adipose tissue (AT)-explants play a role in the paracrine interaction between adipocytes and macrophages, a key mechanism in AT inflammation, leading to metabolic complications like insulin resistance (IR) were determined.Methods: EVs released from in vitro differentiated adipocytes and AT-explants ex vivo were characterized by electron microscopy, Western blot, multiplex adipokine-profiling, and quantified by flow cytometry. Primary monocytes were stimulated with EVs from adipocytes, subcutaneous (SCAT) or omental-derived AT (OAT), and phenotyped. Macrophage supernatant was subsequently used to assess the effect on insulin signaling in adipocytes.Results: Adipocyte and AT-derived EVs differentiated monocytes into macrophages characteristic of human adipose tissue macrophages (ATM), defined by release of both pro- and anti-inflammatory cytokines. The adiponectin-positive subset of AT-derived EVs, presumably representing adipocyte-derived EVs, induced a more pronounced ATM-phenotype than the adiponectin-negative AT-EVs. This effect was more evident for OAT-EVs versus SCAT-EVs. Furthermore, supernatant of macrophages pre-stimulated with AT-EVs interfered with insulin signaling in human adipocytes. Finally, the number of OAT-derived EVs correlated positively with patients HOMA-IR.Conclusions: A possible role for human AT-EVs in a reciprocal pro-inflammatory loop between adipocytes and macrophages, with the potential to aggravate local and systemic IR was demonstrated.