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

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

doi:10.1155/2022/2212996

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

PPAR Res. 2022 Mar 21:2022:2212996. doi: 10.1155/2022/2212996. eCollection 2022.

Authors

Shunli Qi^{1

2}, Qi Yan³, Zhen Wang^{1

4}, Deng Liu^{1

4}, Mengting Zhan^{1

4}, Jian Du^{5

6}, Lijian Chen^{1

4}

Affiliations

¹ Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
² Department of Anesthesiology, Tongling People's Hospital, Tongling 244000, China.
³ School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China.
⁴ Key Laboratory of Anesthesiology and Perioperative Medicine of Anhui Higher Education Institutes, Anhui Medical University, Hefei 230032, China.
⁵ Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China.
⁶ Infectious Disease Research Center, Anhui Medical University, Hefei 230032, China.

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.