中性粒细胞胞外陷阱 (NETs) 调节肥胖人类和小鼠的炎症特征：脂肪组织对 NETs 水平的作用,Molecular Biology Reports

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中性粒细胞胞外陷阱 (NETs) 调节肥胖人类和小鼠的炎症特征：脂肪组织对 NETs 水平的作用
Molecular Biology Reports ( IF 2.6 ) Pub Date : 2022-01-22 , DOI: 10.1007/s11033-022-07157-y
Daniela Fernanda Freitas _{1,

2} , David Fernando Colón ₃ , Rangel Leal Silva ₃ , Eloá Mangabeira Santos ₁ , Victor Hugo Dantas Guimarães ₁ , Guilherme Henrique Mendes Ribeiro ₄ , Alfredo Maurício Batista de Paula ₁ , André Luiz Sena Guimarães ₁ , Sidnei Tavares Dos Reis ₄ , Fernando Queiroz Cunha ₃ , Maisa Mota Antunes ₅ , Gustavo Batista Menezes ₅ , Sérgio Henrique Sousa Santos _{1,

2}

Affiliation

背景

中性粒细胞胞外诱捕器 (NETs) 是最近发现的一种中性粒细胞防御机制，可调节导致代谢谱改变的几种炎症状况。因此，本研究旨在评估肥胖患者和小鼠中 NETs 的产生，验证与脂肪组织释放 NETs 相关的可能机制。

方法和结果

本研究调查了人类脂肪组织中 NETs 的产生，并使用活体显微镜检查小鼠附睾脂肪组织中的中性粒细胞。从富营养化和肥胖个体以及小鼠获得血液和白色脂肪组织。评估了脂质、血糖和白细胞谱，以及 NETs 及其标志物的水平。进行了生物信息学和蛋白质组学分析，并测量了鉴定的关键蛋白质。主要研究结果表明炎症标志物白细胞介素 8 (IL-8)、热休克蛋白 90 (HSP90) 和 E1 热休克蛋白家族 (HSPE1) 可以通过肥胖中的 NETs 水平进行调节。肥胖还与胆固醇升高、葡萄糖耐受不良、离子钙和 NET 相关。我们还观察到过氧化氢酶增加和超氧化物歧化酶活性降低。生物信息学和蛋白质组学分析表明，IL-8、HSP90 和 HSPE1 与肥胖、炎症和 NETs 释放有关。

结论

总之，本研究表明肥胖期间 NETs 产生的增加与脂肪中的重要炎症标志物有关。

图形概要

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Neutrophil extracellular traps (NETs) modulate inflammatory profile in obese humans and mice: adipose tissue role on NETs levels

Background

Neutrophil extracellular traps (NETs) are a recently discovered neutrophil defense mechanism which modulates several inflammatory conditions contributing to metabolic profile alterations. Therefore, the present study aimed to evaluate the production of NETs in obese patients and mice, verifying the possible mechanisms associated with the release of NETs by the adipose tissue.

Methods and results

The present study investigated NETs production in human adipose tissue and also showing the neutrophils using intravital microscopy in mouse epididymal adipose tissue. Blood and white adipose tissues were obtained from eutrophic and obese individuals and from mice. Lipid, glycemic and leukocyte profiles were evaluated, as well as the levels of NETs and its markers. Bioinformatics and proteomics analyses were performed and the identified key proteins were measured. The main findings showed that the inflammatory markers interleukin-8 (IL-8), heat shock protein 90 (HSP90) and the E1 heat shock protein family (HSPE1) can be modulated by the NETs levels in obesity. Obesity has also been associated with increased cholesterol, glucose intolerance, ionic calcium and NETs. We also observed an increase in catalase and a decreased superoxide dismutase activity. Bioinformatics and proteomics analyses revealed that IL-8, HSP90 and HSPE1 were associated with obesity, inflammation and NETs release.