Circulating extracellular vesicles are associated with lipid and insulin metabolism
Circulating extracellular vesicles are associated with lipid and insulin metabolism
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DOI：
10.1152/ajpendo.00160.2018
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发表时间：
2018-10-01
影响因子：
5.1
通讯作者：
Taguchi, Osamu
中科院分区：
文献类型：
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作者：
Kobayashi, Yoshinao;Eguchi, Akiko;Taguchi, Osamu
我们报道，在一项针对肥胖患者的初步研究中，肥大的脂肪细胞释放细胞外囊泡（EV），并且循环脂肪细胞衍生的 EV 的数量与胰岛素和稳态模型评估胰岛素抵抗（HOMA-IR）相关。在这里，我们探讨了 203 名接受 75 克口服葡萄糖耐量试验 (OGTT) 的受试者（76 名男性和 127 名女性；中位年龄 54 岁）的循环 EV 水平与各种代谢参数（包括肥胖、脂质和葡萄糖代谢）之间的关联，这些受试者有或没有代谢疾病危险因素。男性循环 EV 数显着高于女性 (P < 0.001)。 OGTT 模式受损的个体的循环 EV 数量显着高于 OGTT 模式正常的个体（P < 0.05）。多元回归分析显示，循环 EV 数与甘油三酯升高的相关性最强且显着（TG；t = 8.55，P < 0.001）。此外，循环 EV 数量与稳态模型评估 - β 细胞功能显着相关（HOMA-β；t = 2.38，P < 0.05）。受试者工作特征曲线显示，血清 TG 水平升高（≥ 150 mg/dl）个体的 EV 数截止值已确定（136,738 EVs/μl 血浆，P < 0.001，敏感性 0.842，假阳性率为 0.257）。在部分分离的循环EV上检测到Perilipin和脱唾液酸糖蛋白受体1，表明脂肪细胞和肝细胞释放EV，这与脂质和葡萄糖代谢有关。循环 EV 代表了一种有前途的脂质和葡萄糖代谢代谢生物标志物，并且具有监测人类代谢状态的潜力，包括没有代谢危险因素的个体。
We have reported that hypertrophic adipocytes release extracellular vesicles (EVs) and the number of circulating adipocyte-derived EVs correlated with insulin and homeostasis model assessment-insulin resistance (HOMA-IR) in a pilot study using obese patients. Here, we explored the association between circulating EV level and various metabolic parameters, including obesity and lipid and glucose metabolisms, among 203 subjects (76 men and 127 women; median age, 54 yr) with or without risk factor for metabolic diseases, who received a 75-g oral glucose tolerance test (OGTT). Circulating EV number was significantly higher in men than in women (P < 0.001). Circulating EV number in individuals with impaired OGTT pattern was significantly higher compared with those with normal OGTT patterns (P < 0.05). Multiple regression analysis revealed that circulating EV number correlated most strongly and significantly with elevated triglyceride (TG; t = 8.55, P < 0.001). Additionally, circulating EV number correlated significantly with homeostasis model assessment-beta-cell function (HOMA-beta; t = 2.38, P < 0.05). Receiver operating characteristic curve revealed that the cutoff value of EV numbers in individuals with elevated serum TG levels (>= 150 mg/dl) was identified (136,738 EVs/mu l of plasma, P < 0.001, sensitivity 0.842, false-positive rate of 0.257). Perilipin and asialoglycoprotein receptor 1 were detected on a part of isolated circulating EVs, indicating EV release from adipocytes and hepatocytes, which were related to lipid and glucose metabolism. Circulating EVs represent a promising metabolic biomarker for lipid and glucose metabolism and have potential for monitoring metabolic status in humans, including individuals without metabolic risk factors.