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.
Shunli Qi  1  2 ,  Qi Yan  3 ,  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.
PMID: 35356086 DOI: 10.1155/2022/2212996
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.

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