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
Affiliations
Jianbin Bi
National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, China; Institute of Advanced Surgical Technology and Engineering, China; Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, China
Jia Zhang
National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, China; Institute of Advanced Surgical Technology and Engineering, China; Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, China
Yifan Ren
National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, China; Institute of Advanced Surgical Technology and Engineering, China; Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, China
Zhaoqing Du
National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, China; Institute of Advanced Surgical Technology and Engineering, China; Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, China
Qingshan Li
National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, China; Institute of Advanced Surgical Technology and Engineering, China; Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, China
Yue Wang
National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, China; Institute of Advanced Surgical Technology and Engineering, China; Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, China
Shasha Wei
National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, China; Institute of Advanced Surgical Technology and Engineering, China
Lifei Yang
National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, China; Institute of Advanced Surgical Technology and Engineering, China
Jingyao Zhang
Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, China
Chang Liu
Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, China
Yi Lv
National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, China; Institute of Advanced Surgical Technology and Engineering, China; Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, China
Rongqian Wu
National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, China; Institute of Advanced Surgical Technology and Engineering, China; Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, China; Correspondence to: Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi’an Jiaotong University, 76 West Yanta Road, P.O. Box 124, Xi’an, Shaanxi Province 710061, China.
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. Keywords: Hepatic I/R, Irisin, Mitochondrial homeostasis, Oxidative stress
