脂肪组织
脂联素
脂肪因子
炎症
液体活检
胞外囊泡
小RNA
细胞外小泡
微泡
细胞生物学
肥胖
生物
化学
生物信息学
内科学
医学
内分泌学
生物化学
瘦素
基因
胰岛素抵抗
癌症
作者
Sandipan Mishra,Ashish Kumar,Susy Kim,Yixin Su,Sangeeta Singh,Mitu Sharma,Sameh Almousa,Hilal Rather,Hemani Jain,Jingyun Lee,Cristina M. Furdui,Sarfaraz Ahmad,Carlos M. Ferrario,Henry Punzi,Chia‐Chi Chuang,Martin Wabitsch,Stephen B. Kritchevsky,Thomas C. Register,Gagan Deep
出处
期刊:ACS Nano
[American Chemical Society]
日期:2023-05-24
卷期号:17 (11): 10252-10268
被引量:2
标识
DOI:10.1021/acsnano.3c00422
摘要
Obesity is a major risk factor for multiple chronic diseases. Anthropometric and imaging approaches are primarily used to assess adiposity, and there is a dearth of techniques to determine the changes in adipose tissue (AT) at the molecular level. Extracellular vesicles (EVs) have emerged as a novel and less invasive source of biomarkers for various pathologies. Furthermore, the possibility of enriching cell or tissue-specific EVs from the biofluids based on their unique surface markers has led to classifying these vesicles as "liquid biopsies", offering valuable molecular information on hard-to-access tissues. Here, we isolated small EVs from AT (sEVAT) of lean and diet-induced obese (DIO) mice, identified unique surface proteins on sEVAT by surface shaving followed by mass spectrometry, and developed a signature of five unique proteins. Using this signature, we pulled out sEVAT from the blood of mice and validated the specificity of isolated sEVAT by measuring the expression of adiponectin, 38 adipokines on an array, and several adipose tissue-related miRNAs. Furthermore, we provided evidence of sEV applicability in disease prediction by characterizing sEVAT from the blood of lean and DIO mice. Interestingly, sEVAT-DIO cargo showed a stronger pro-inflammatory effect on THP1 monocytes compared to sEVAT-Lean and a significant increase in obesity-associated miRNA expression. Equally important, sEVAT cargo revealed an obesity-associated aberrant amino acid metabolism that was subsequently validated in the corresponding AT. Lastly, we show a significant increase in inflammation-related molecules in sEVAT isolated from the blood of nondiabetic obese (>30 kg/m2) individuals. Overall, the present study offers a less-invasive approach to characterize AT.
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