Neutrophil activation at high-fat high-cholesterol and high-fructose diets induces low-grade inflammation in mice

G. Bila, O. Vishchur, V. Vovk, S. Vari, R. Bilyy
{"title":"Neutrophil activation at high-fat high-cholesterol and high-fructose diets induces low-grade inflammation in mice","authors":"G. Bila, O. Vishchur, V. Vovk, S. Vari, R. Bilyy","doi":"10.15407/ubj96.02.027","DOIUrl":null,"url":null,"abstract":"Nonalcoholic fatty liver disease (NAFLD), which can progress to nonalcoholic steatohepatitis (NASH), is a significant health concern affecting a substantial portion of the population. This study investigates the role of neutrophil extracellular traps (NETs) in liver inflammation induced by high-fat high-cholesterol diet (HFHCD) and high-fructose diet (HFD). The chronic nature of NAFLD involves low-grade inflammation with cytokine elevation. The research aims to visualize neutrophil elastase (NE) activity during HFHCD and HFD representing conditions of low-grade activation and assess neutrophil functional status. The study employs a mouse model subjecting animals to HFHCD, HFD or a standard diet (SD) for six weeks. Various analyses were used including histological evaluations, in vivo imaging of NE activity using a fluorescent probe, fluorescent microscopy, flow cytometry and assessment of neutrophil function through reactive oxygen species (ROS) levels. Mice on HFHCD and HFD display liver damage consistent with NASH, which was validated pathohistologically. NE activity in blood significantly increases after six weeks indicating systemic NETs involvement. In vivo imaging confirms NE activity in multiple organs. Cellular localization reveals NETs persistence even after neutrophil destruction in splenocytes indicating systemic involvement. Neutrophils under HFHCD exhibit a functional phenotype associated with low-grade inflammation, higher basal ROS levels and reduced activation potential. This study establishes the systemic impact of NETs in HFHCD- and HFD-induced liver inflammation, providing insights into the functional state of neutrophils. The findings contribute to understanding the mechanisms underlying chronic liver conditions and may inform future therapeutic strategies. Keywords: high fat diet, in vivo imaging, low-grade inflammation, NASH, neutrophil elastase, neutrophil extracellular traps, neutrophils","PeriodicalId":23007,"journal":{"name":"The Ukrainian Biochemical Journal","volume":"68 24","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Ukrainian Biochemical Journal","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.15407/ubj96.02.027","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Nonalcoholic fatty liver disease (NAFLD), which can progress to nonalcoholic steatohepatitis (NASH), is a significant health concern affecting a substantial portion of the population. This study investigates the role of neutrophil extracellular traps (NETs) in liver inflammation induced by high-fat high-cholesterol diet (HFHCD) and high-fructose diet (HFD). The chronic nature of NAFLD involves low-grade inflammation with cytokine elevation. The research aims to visualize neutrophil elastase (NE) activity during HFHCD and HFD representing conditions of low-grade activation and assess neutrophil functional status. The study employs a mouse model subjecting animals to HFHCD, HFD or a standard diet (SD) for six weeks. Various analyses were used including histological evaluations, in vivo imaging of NE activity using a fluorescent probe, fluorescent microscopy, flow cytometry and assessment of neutrophil function through reactive oxygen species (ROS) levels. Mice on HFHCD and HFD display liver damage consistent with NASH, which was validated pathohistologically. NE activity in blood significantly increases after six weeks indicating systemic NETs involvement. In vivo imaging confirms NE activity in multiple organs. Cellular localization reveals NETs persistence even after neutrophil destruction in splenocytes indicating systemic involvement. Neutrophils under HFHCD exhibit a functional phenotype associated with low-grade inflammation, higher basal ROS levels and reduced activation potential. This study establishes the systemic impact of NETs in HFHCD- and HFD-induced liver inflammation, providing insights into the functional state of neutrophils. The findings contribute to understanding the mechanisms underlying chronic liver conditions and may inform future therapeutic strategies. Keywords: high fat diet, in vivo imaging, low-grade inflammation, NASH, neutrophil elastase, neutrophil extracellular traps, neutrophils
高脂肪高胆固醇和高果糖饮食诱发小鼠低度炎症的中性粒细胞活化
非酒精性脂肪肝(NAFLD)可发展为非酒精性脂肪性肝炎(NASH),是影响相当一部分人健康的重大问题。本研究调查了中性粒细胞胞外捕获物(NET)在高脂高胆固醇饮食(HFHCD)和高果糖饮食(HFD)诱导的肝脏炎症中的作用。非酒精性脂肪肝的慢性性质包括细胞因子升高的低度炎症。该研究旨在观察高脂高胆固醇饮食(HFHCD)和高果糖饮食(HFD)期间代表低度激活状态的中性粒细胞弹性蛋白酶(NE)活性,并评估中性粒细胞的功能状态。研究采用了一种小鼠模型,对动物进行为期六周的高频高密度脂蛋白胆固醇饮食(HFHCD)、高频高密度脂蛋白胆固醇饮食(HFD)或标准饮食(SD)。研究采用了多种分析方法,包括组织学评估、使用荧光探针对中性粒细胞活性进行体内成像、荧光显微镜、流式细胞术以及通过活性氧(ROS)水平评估中性粒细胞功能。服用高密度脂蛋白胆固醇和高密度脂蛋白胆固醇饮食的小鼠显示出与 NASH 一致的肝损伤,病理组织学对此进行了验证。血液中的 NE 活性在六周后明显增加,表明有全身性 NETs 参与。体内成像证实了 NE 在多个器官中的活性。细胞定位显示,即使脾细胞中的中性粒细胞被破坏,NETs 仍会持续存在,这表明NETs 涉及全身。高频高密度脂蛋白血症患者的中性粒细胞表现出与低度炎症、较高的基础 ROS 水平和较低的活化潜能相关的功能表型。这项研究确定了NET在HFHCD和HFD诱导的肝脏炎症中的系统性影响,为深入了解中性粒细胞的功能状态提供了依据。这些发现有助于了解慢性肝病的发病机制,并为未来的治疗策略提供参考。关键词:高脂饮食;体内成像;低度炎症;NASH;中性粒细胞弹性蛋白酶;中性粒细胞胞外捕获器;中性粒细胞
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信