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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.00597

Adiponectin Protects against Cerebral Ischemic Injury through AdipoR1/AMPK pathways

 Bin Liu1, Jing Liu1, Jiangong Wang1, Fengjiao Sun1, Shujun Jiang1, Fengai Hu1,  Dan Wang1, Dunjiang Liu1, Cuilan Liu1 and  Haijing Yan1*
  • 1Binzhou Medical University Hospital, China

Excitotoxicity induced by excessive NMDA receptor activation underlies the pathology of ischemic injury. Adiponectin (APN) is an adipocyte-derived protein hormone that modulates a number of metabolic processes. APN exerts a wide range of biological functions in the central nervous system. However, the role of adiponectin and its receptors in cerebral ischemia/reperfusion-induced injury and the related mechanisms remain to be clarified. Here we found that APN and APN receptor agonist AdipoRon (APR) were protective against excitotoxicity induced by oxygen and glucose deprivation / reperfusion (OGD/R) and NMDA in primary neurons. Adiponectin receptor 1 (AdipoR1) knock down reversed the protection conferred by either APN or APR. Moreover, the protective effects offered by both APN and APR were compromised by Compound C, an inhibitor of AMPK phosphorylation. Both APN and APR protected the dissipation of the ΔΨm caused by OGD/R. They also up-regulated the PGC-1 expression, which was reversed by Compound C. Furthermore, both APN and APR ameliorated but APN knock out aggravated the infarct volume and neurological deficient induced by transient middle cerebral artery occlusion (tMCAO) in vivo. Taken together, these findings show that APN and APR protect against ischemic injury in vitro and in vivo. The protective mechanism is mainly related to AdipoR1 dependent AMPK phosphorylation and PGC-1alpha up-regulation.

Keywords: Adiponectin, Adiporon, AdipoR1, cerebral ischemia, AMPK, PGC-1 alpha, mitochondrial

Received: 08 Mar 2019; Accepted: 09 May 2019.

Edited by:

Salvatore Salomone, Università degli Studi di Catania, Italy

Reviewed by:

Howard Prentice, Florida Atlantic University, United States
Helena Domin, Institute of Pharmacology, Polish Academy of Sciences, Poland  

Copyright: © 2019 Liu, Liu, Wang, Sun, Jiang, Hu, Wang, Liu, Liu and Yan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Haijing Yan, Binzhou Medical University Hospital, Binzhou, China, hjyan211@163.com