Oleoylethanolamide Alleviates Hepatic Ischemia-Reperfusion Injury via Inhibiting Endoplasmic Reticulum Stress-Associated Apoptosis

IF 3.5 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

PPAR Research Pub Date : 2022-03-21 DOI:10.1155/2022/2212996

Shunli Qi, Qi Yan, Zhen Wang, Deng Liu, Mengting Zhan, Jian Du, Lijian Chen

{"title":"Oleoylethanolamide Alleviates Hepatic Ischemia-Reperfusion Injury via Inhibiting Endoplasmic Reticulum Stress-Associated Apoptosis","authors":"Shunli Qi, Qi Yan, Zhen Wang, Deng Liu, Mengting Zhan, Jian Du, Lijian Chen","doi":"10.1155/2022/2212996","DOIUrl":null,"url":null,"abstract":"Liver ischemia/reperfusion (I/R) injury is a primary complication in major liver surgery. Our previous study about proteome profiling has revealed that the PPAR signaling cascade was significantly upregulated during liver ischemia/reperfusion. To elucidate the potential mechanisms of PPARα involved in I/R injury, we used oleoylethanolamide (OEA), the peroxisome proliferator-activated receptor alpha (PPARα) agonist, in this study. We demonstrated a protective role of OEA on liver I/R injury by using a mouse model of partial warm ischemia-reperfusion and hypoxia-reoxygenation model of hepatocytes. These effects were caused by ameliorating liver damage, decreasing the level of serum ALT and AST, and reducing the apoptosis of hepatocytes. Furthermore, a mechanistic study revealed that OEA regulated endoplasmic reticulum (ER) stress by activating PPARα, thereby reducing ER stress-associated apoptosis to attenuate liver I/R injury. Briefly, these data first proposed that OEA-mediated PPARα activation could be an effective therapy against hepatic ischemia/reperfusion injury.","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":" ","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2022-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"PPAR Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1155/2022/2212996","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}

引用次数: 2

Abstract

Liver ischemia/reperfusion (I/R) injury is a primary complication in major liver surgery. Our previous study about proteome profiling has revealed that the PPAR signaling cascade was significantly upregulated during liver ischemia/reperfusion. To elucidate the potential mechanisms of PPARα involved in I/R injury, we used oleoylethanolamide (OEA), the peroxisome proliferator-activated receptor alpha (PPARα) agonist, in this study. We demonstrated a protective role of OEA on liver I/R injury by using a mouse model of partial warm ischemia-reperfusion and hypoxia-reoxygenation model of hepatocytes. These effects were caused by ameliorating liver damage, decreasing the level of serum ALT and AST, and reducing the apoptosis of hepatocytes. Furthermore, a mechanistic study revealed that OEA regulated endoplasmic reticulum (ER) stress by activating PPARα, thereby reducing ER stress-associated apoptosis to attenuate liver I/R injury. Briefly, these data first proposed that OEA-mediated PPARα activation could be an effective therapy against hepatic ischemia/reperfusion injury.

查看原文本刊更多论文

油基乙醇酰胺通过抑制内质网应激相关细胞凋亡减轻肝缺血再灌注损伤

肝缺血/再灌注(I/R)损伤是肝脏大手术的主要并发症。我们之前关于蛋白质组分析的研究表明，PPAR信号级联在肝脏缺血/再灌注过程中显著上调。为了阐明PPARα参与I/R损伤的潜在机制，我们在本研究中使用了油基乙醇酰胺(OEA)，过氧化物酶体增殖物激活受体α (PPARα)激动剂。我们通过小鼠部分热缺血-再灌注和肝细胞缺氧-再氧化模型证明了OEA对肝脏I/R损伤的保护作用。这些作用是通过改善肝损伤，降低血清ALT和AST水平，减少肝细胞凋亡引起的。此外，一项机制研究表明，OEA通过激活PPARα来调节内质网(ER)应激，从而减少内质网应激相关的细胞凋亡，从而减轻肝脏I/R损伤。简而言之，这些数据首次提出了oea介导的PPARα激活可能是治疗肝脏缺血/再灌注损伤的有效方法。

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

PPAR Research MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

6.20

自引率

3.40%

发文量

审稿时长

12 months

期刊介绍： PPAR Research is a peer-reviewed, Open Access journal that publishes original research and review articles on advances in basic research focusing on mechanisms involved in the activation of peroxisome proliferator-activated receptors (PPARs), as well as their role in the regulation of cellular differentiation, development, energy homeostasis and metabolic function. The journal also welcomes preclinical and clinical trials of drugs that can modulate PPAR activity, with a view to treating chronic diseases and disorders such as dyslipidemia, diabetes, adipocyte differentiation, inflammation, cancer, lung diseases, neurodegenerative disorders, and obesity.