Center for Physical and Mental Health, Mie University Graduate School of Medicine, Tsu, Japan.
Department of Gastroenterology and Hepatology, Mie University Graduate School of Medicine, Tsu, Japan.
Am J Physiol Endocrinol Metab. 2018 Oct 1;315(4):E574-E582. doi: 10.1152/ajpendo.00160.2018. Epub 2018 Jun 26.
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-β-cell function (HOMA-β; 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/μl 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.
我们曾报道过，肥大脂肪细胞会释放细胞外囊泡（EVs），并且在使用肥胖患者的初步研究中，循环脂肪细胞衍生 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，我们在 203 名有或没有代谢疾病风险因素的受试者（76 名男性和 127 名女性；中位年龄 54 岁）中探索了循环 EV 水平与各种代谢参数之间的关联，这些受试者接受了 75g 口服葡萄糖耐量试验（OGTT）。男性的循环 EV 数量明显高于女性（P < 0.001）。糖耐量异常个体的循环 EV 数量明显高于糖耐量正常个体（P < 0.05）。多元回归分析显示，循环 EV 数量与升高的甘油三酯（TG）相关性最强且最显著（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（HOMA-β）显著相关（t = 2.38，P < 0.05）。ROC 曲线显示，在 TG 水平升高（≧150mg/dl）的个体中，EV 数量的截断值被确定（136738EVs/μl 血浆，P < 0.001，敏感性 0.842，假阳性率 0.257）。在部分分离的循环 EV 上检测到 perilipin 和去唾液酸糖蛋白受体 1，表明 EV 是从脂肪细胞和肝细胞中释放的，这与脂质和葡萄糖代谢有关。循环 EV 是脂质和葡萄糖代谢的有前途的代谢生物标志物，并且有可能监测包括无代谢风险因素的个体在内的人类的代谢状态。
