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肥胖女性与非肥胖女性血浆膜衍生细胞外囊泡的比较和功能分析。

Comparative and functional analysis of plasma membrane-derived extracellular vesicles from obese vs. nonobese women.

机构信息

Group of Translational Research in Respiratory Medicine, Hospital Universitari Arnau de Vilanova y Santa Maria, IRB Lleida, Lleida, Spain.

Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Department of Diabetes, Endocrinology, and Nutrition (UDEN), Institut d'Investigació Biomédica de Girona (IdIBGi), Girona, Spain.

出版信息

Clin Nutr. 2020 Apr;39(4):1067-1076. doi: 10.1016/j.clnu.2019.04.008. Epub 2019 Apr 17.

DOI:10.1016/j.clnu.2019.04.008
PMID:31036413
Abstract

BACKGROUND

Membrane-derived extracellular vesicles (EVs) are released to the circulation by cells found in adipose tissue, transferring microRNAs (miRNAs) that may mediate the adaptive response of recipient cells. This study investigated plasma EVs from obese vs. nonobese women and their functional impact in adipocytes.

METHODS

Plasma EVs were isolated by differential centrifugation. Concentration and size were examined by nanoparticle tracking analysis (NanoSight). RNA was purified from plasma and plasma EVs of 45 women (47 ± 12 years, 58% of obesity) and profiles of mature miRNAs were assessed. Functional analyses were performed in human adipocytes.

FINDINGS

Smaller plasma EVs were found in obese when compared to nonobese women. Positive associations were identified between circulating EVs numbers and parameters of impaired glucose tolerance. Almost 40% of plasma cell-free miRNAs were also found in isolated plasma EVs, defined as Ct values < 37 in ≥75% of samples. BMI together with parameters of insulin resistance were major contributors to EVs-contained miRNA patterns. Treatments of cultured human adipocytes with EVs from obese women led to a significant reduction of genes involved in lipid biosynthesis, while increasing the expression of IRS1 (12.3%, p = 0.002).

INTERPRETATION

Size, concentration and the miRNA cargo of plasma EVs are associated with obesity and parameters of insulin resistance. Plasma EVs may mediate intercellular communication relevant to metabolism in adipocytes.

摘要

背景

细胞外囊泡(EVs)是由脂肪组织中的细胞释放到循环中的,它们传递的 microRNAs(miRNAs)可能介导受体细胞的适应性反应。本研究调查了肥胖与非肥胖女性的血浆 EVs 及其在脂肪细胞中的功能影响。

方法

通过差速离心分离血浆 EVs。通过纳米颗粒跟踪分析(NanoSight)检测浓度和大小。从 45 名女性(47±12 岁,肥胖率为 58%)的血浆和血浆 EVs 中纯化 RNA,并评估成熟 miRNA 的谱。在人脂肪细胞中进行功能分析。

结果

与非肥胖女性相比,肥胖女性的血浆 EVs 更小。循环 EVs 数量与糖耐量受损参数之间存在正相关。几乎 40%的循环无细胞 miRNA 也存在于分离的血浆 EVs 中,定义为≥75%的样本中 Ct 值<37。BMI 与胰岛素抵抗参数是 EVs 中 miRNA 模式的主要贡献者。用肥胖女性的 EVs 处理培养的人脂肪细胞,导致参与脂质生物合成的基因显著减少,而 IRS1 的表达增加(12.3%,p=0.002)。

结论

血浆 EVs 的大小、浓度和 miRNA 载量与肥胖和胰岛素抵抗参数相关。血浆 EVs 可能介导与脂肪细胞代谢相关的细胞间通讯。

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