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γ-谷维素作为一种潜在的过氧化物酶体增殖物激活受体-γ调节剂在脂肪组织中通过调节氧化应激和炎症:COVID-19 细胞因子风暴的假设治疗方法?

Gamma-oryzanol as a potential modulator of oxidative stress and inflammation via PPAR-y in adipose tissue: a hypothetical therapeutic for cytokine storm in COVID-19?

机构信息

São Paulo State University (Unesp), Medical School, Botucatu, São Paulo, Brazil.

São Paulo State University (Unesp), Medical School, Botucatu, São Paulo, Brazil.

出版信息

Mol Cell Endocrinol. 2021 Jan 15;520:111095. doi: 10.1016/j.mce.2020.111095. Epub 2020 Nov 28.

Abstract

UNLABELLED

The literature has reported a higher prevalence of negative clinical outcomes due to Coronavirus disease 19 (COVID-19) in obese individuals. This can be explained by the cytokine storm, result from the cytokine production from both obesity and viral infection. Gamma-oryzanol (γOz) is a compound with anti-inflammatory and antioxidant activities. However, little is known about the γOz action as a possible agonist of peroxisome proliferator-activated receptor gamma (PPAR-γ). The aim of this study was to test the hypothesis that γOz attenuates the cytokine storm by stimulating PPAR-γ in the adipose tissue.

METHODS

Male Wistar rats were randomly divided into three experimental groups and fed ad libitum for 30 weeks with control diet (C, n = 6), high sugar-fat diet (HSF, n = 6) or high sugar-fat diet + γOz (HSF + γOz, n = 6). HSF groups also received water + sucrose (25%). The γOz dose was 0.5% in the chow. Evaluation in animals included caloric intake, body weight, adiposity index, plasma triglycerides, and HOMA-IR. In adipose tissue was evaluated: PPAR-γ gene and protein expression, inflammatory and oxidative stress parameters, and histological analysis.

RESULTS

Adipose tissue dysfunction was observed in HSF group, which presented remarkable PPAR-γ underexpression and increased levels of cytokines, other inflammatory markers and oxidative stress. The γOz treatment prevented adipose tissue dysfunction and promoted PPAR-γ overexpression.

CONCLUSION

Natural compounds as γOz can be considered a coadjutant therapy to prevent the cytokine storm in COVID-19 patients with obesity conditions.

摘要

目的

本研究旨在通过刺激脂肪组织中的过氧化物酶体增殖物激活受体γ(PPAR-γ),验证γ-谷维素(γOz)通过抑制细胞因子风暴减轻肥胖 COVID-19 患者炎症反应的假说。

方法

雄性 Wistar 大鼠随机分为三组,分别给予对照饮食(C 组,n=6)、高糖高脂饮食(HSF 组,n=6)或高糖高脂饮食+γ-谷维素(HSF+γOz 组,n=6),自由进食 30 周。HSF 组还给予水+蔗糖(25%)。饮食中γ-谷维素的剂量为 0.5%。对动物进行能量摄入、体重、肥胖指数、血浆甘油三酯和 HOMA-IR 评估。评估脂肪组织中的 PPAR-γ 基因和蛋白表达、炎症和氧化应激参数以及组织学分析。

结果

HSF 组观察到脂肪组织功能障碍,表现为 PPAR-γ 明显低表达和细胞因子、其他炎症标志物和氧化应激水平升高。γOz 治疗可预防脂肪组织功能障碍并促进 PPAR-γ 过表达。

结论

天然化合物如γ-谷维素可作为肥胖 COVID-19 患者细胞因子风暴的辅助治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8241/7695949/5ed85c68d9fd/gr1_lrg.jpg

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