Circulating extracellular vesicles are associated with lipid and insulin metabolism

Kobayashi, Yoshinao, Akiko Eguchi, Mina Tempaku, Tatsuro Honda, Kenji Togashi, Motoh Iwasa, Hiroshi Hasegawa, Yoshiyuki Takei, Yasuhiro Sumida, and Osamu Taguchi. "Circulating extracellular vesicles are associated with lipid and insulin metabolism." American Journal of Physiology-Endocrinology and Metabolism (2018).

We have reported that hypertrophic adipocytes release extracellular vesicles (EVs) and that 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, 127 women; median age, 54 years) 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 to those with normal OGTT pattern (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-β) (t=2.38, p<0.05). Receiver operating characteristic curve revealed the cut off value of EV numbers in individuals with elevated serum TG levels (≧ 150mg/dL) was identified (136,738 EVs/μl of plasma, p<0.001, sensitivity 0.842, false positive rate 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.

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