Irisin alleviates liver ischemia-reperfusion injury by inhibiting excessive mitochondrial fission, promoting mitochondrial biogenesis and decreasing oxidative stress

Jianbin Bi,Jia Zhang,Yifan Ren,Zhaoqing Du,Qingshan Li,Yue Wang,Shasha Wei,Lifei Yang,Jingyao Zhang,Chang Liu,Yi Lv,Rongqian Wu

doi:10.1016/j.redox.2018.10.019

Abstract

Current management of liver ischemia-reperfusion (I/R) injury is mainly based on supportive care and no specific treatment is available. Irisin, a recently identified hormone, plays pivotal roles in energy expenditure and oxidative metabolism; however, it remains unknown whether irisin has any protective effects on hepatic I/R injury. In this study, we found that serum and liver irisin levels were markedly decreased at 24 h after hepatic I/R. Treatment with exogenous irisin improved liver function, reduced liver necrosis and cell apoptosis, and relieved inflammatory response after hepatic I/R. Meanwhile, exogenous irisin markedly inhibited mitochondrial fission related protein dynamin related protein 1 (drp-1) and fission 1 (Fis-1) expression in hepatic I/R. Additionally, treatment with exogenous irisin increased mitochondrial content and increased mitochondrial biogenesis related peroxisome proliferative activated receptor-γ (PPARγ) co-activator 1α (PGC-1α) and mitochondrial transcription factor (TFAM) expression. Furthermore, irisin decreased oxidative stress by upregulating uncoupling proteins (UCP) 2 expression in hepatic I/R. The results reveal that treatment with exogenous irisin alleviated hepatic I/R injury by restraining mitochondrial fission, promoting mitochondrial biogenesis and relieving oxidative stress. Irisin treatment appears to be a novel and promising therapeutic approach for hepatic I/R injury.

Highlights

Liver ischemia-reperfusion (I/R) injury is a major cause of hepatic dysfunction or failure following liver resection, liver transplantation, hemorrhagic shock, severe sepsis and so on [1]
We showed that treatment with exogenous irisin alleviated hepatic I/R injury in mice
The potential mechanisms might be related to irisin's role in inhibiting excessive mitochondrial fission, promoting mitochondrial biogenesis and decreasing oxidative stress

Summary

Introduction

Liver ischemia-reperfusion (I/R) injury is a major cause of hepatic dysfunction or failure following liver resection, liver transplantation, hemorrhagic shock, severe sepsis and so on [1]. Excessive reactive oxygen species (ROS), massive inflammatory mediators and mitochondrial dysfunction during the reperfusion trigger apoptosis and hepatic dysfunction [2,3]. Excessive mitochondrial fission leads to mitochondrial fragmentation and activates the cell apoptosis pathway, which aggravates tissue injury [6]. Mitochondrial biogenesis is severely decreased in hepatic I/R [7]. Decreased expression of uncoupling proteins (UCP) results in excessive ROS can directly damage mitochondrial DNA (mtDNA), leading to mitochondrial dysfunction and subsequent depletion of ATP and cell death [9,10]

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