Inhibiting TRIM8 alleviates adipocyte inflammation and insulin resistance by regulating the DUSP14/MAPKs pathway.

IF 3.5 4区 生物学 Q2 ENDOCRINOLOGY & METABOLISM
Adipocyte Pub Date : 2024-12-01 Epub Date: 2024-07-22 DOI:10.1080/21623945.2024.2381262
Mingxue Zhu, Junliang Pu, Ting Zhang, Huarui Shao, Rui Su, Chengyong Tang
{"title":"Inhibiting TRIM8 alleviates adipocyte inflammation and insulin resistance by regulating the DUSP14/MAPKs pathway.","authors":"Mingxue Zhu, Junliang Pu, Ting Zhang, Huarui Shao, Rui Su, Chengyong Tang","doi":"10.1080/21623945.2024.2381262","DOIUrl":null,"url":null,"abstract":"<p><p>Obesity is a low-grade chronic inflammation induced by the pathological expansion of adipocytes which allows the development of obesity-associated metabolic diseases like type 2 diabetes mellitus (T2D) and non-alcoholic fatty liver disease (NAFLD). However, mechanisms regulating adipocyte inflammation remain poorly understood. Here, we observed that TRIM8 was upregulated in adipocyte inflammation and insulin resistance while DUSP14 was downregulated. TRIM8 deficiency and DUSP14 over-expression decreased the level of inflammatory cytokines, increased glucose uptake content, and improved insulin signalling transduction compared to LPS treatment alone. Conversely, silencing DUSP14 increased the expression of inflammatory cytokines. It decreased the glucose uptake content and the phosphorylation level of proteins involved in insulin signalling, further impairing insulin signalling and aggravating insulin resistance. Furthermore, The decreased level of inflammatory cytokines, increased glucose uptake, and improved insulin signalling transduction caused by TRIM8 deficiency were reversed by down-regulated DUSP14. Collectively, our findings revealed that TRIM8 can regulate adipocyte inflammation and insulin resistance by regulating the MAPKs pathway which is dependent on DUSP14.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11268219/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Adipocyte","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/21623945.2024.2381262","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/22 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0

Abstract

Obesity is a low-grade chronic inflammation induced by the pathological expansion of adipocytes which allows the development of obesity-associated metabolic diseases like type 2 diabetes mellitus (T2D) and non-alcoholic fatty liver disease (NAFLD). However, mechanisms regulating adipocyte inflammation remain poorly understood. Here, we observed that TRIM8 was upregulated in adipocyte inflammation and insulin resistance while DUSP14 was downregulated. TRIM8 deficiency and DUSP14 over-expression decreased the level of inflammatory cytokines, increased glucose uptake content, and improved insulin signalling transduction compared to LPS treatment alone. Conversely, silencing DUSP14 increased the expression of inflammatory cytokines. It decreased the glucose uptake content and the phosphorylation level of proteins involved in insulin signalling, further impairing insulin signalling and aggravating insulin resistance. Furthermore, The decreased level of inflammatory cytokines, increased glucose uptake, and improved insulin signalling transduction caused by TRIM8 deficiency were reversed by down-regulated DUSP14. Collectively, our findings revealed that TRIM8 can regulate adipocyte inflammation and insulin resistance by regulating the MAPKs pathway which is dependent on DUSP14.

抑制 TRIM8 可通过调节 DUSP14/MAPKs 通路缓解脂肪细胞炎症和胰岛素抵抗。
肥胖症是一种由脂肪细胞病理性扩张诱发的低度慢性炎症,可导致 2 型糖尿病(T2D)和非酒精性脂肪肝(NAFLD)等与肥胖相关的代谢性疾病的发生。然而,人们对脂肪细胞炎症的调控机制仍然知之甚少。在这里,我们观察到 TRIM8 在脂肪细胞炎症和胰岛素抵抗中上调,而 DUSP14 则下调。与单独使用LPS处理相比,TRIM8缺乏和DUSP14过度表达可降低炎症细胞因子水平、增加葡萄糖摄取含量并改善胰岛素信号转导。相反,沉默 DUSP14 会增加炎性细胞因子的表达。它降低了葡萄糖摄取量和参与胰岛素信号转导的蛋白质的磷酸化水平,进一步损害了胰岛素信号转导,加重了胰岛素抵抗。此外,TRIM8 缺乏导致的炎性细胞因子水平下降、葡萄糖摄取量增加和胰岛素信号转导改善被下调的 DUSP14 所逆转。总之,我们的研究结果表明,TRIM8 可通过调节依赖于 DUSP14 的 MAPKs 通路来调节脂肪细胞炎症和胰岛素抵抗。
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
Adipocyte
Adipocyte Medicine-Histology
CiteScore
6.50
自引率
3.00%
发文量
46
审稿时长
32 weeks
期刊介绍: Adipocyte recognizes that the adipose tissue is the largest endocrine organ in the body, and explores the link between dysfunctional adipose tissue and the growing number of chronic diseases including diabetes, hypertension, cardiovascular disease and cancer. Historically, the primary function of the adipose tissue was limited to energy storage and thermoregulation. However, a plethora of research over the past 3 decades has recognized the dynamic role of the adipose tissue and its contribution to a variety of physiological processes including reproduction, angiogenesis, apoptosis, inflammation, blood pressure, coagulation, fibrinolysis, immunity and general metabolic homeostasis. The field of Adipose Tissue research has grown tremendously, and Adipocyte is the first international peer-reviewed journal of its kind providing a multi-disciplinary forum for research focusing exclusively on all aspects of adipose tissue physiology and pathophysiology. Adipocyte accepts high-profile submissions in basic, translational and clinical research.
×
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