Excessive irisin increases oxidative stress and apoptosis in murine heart

Ming Yun Ho, Ming Shien Wen*, Jih Kai Yeh, I. Chang Hsieh, Chun Chi Chen, Ming Jer Hsieh, Ming Lung Tsai, Chia Hung Yang, Victor Chien Chia Wu, Kuo Chun Hung, Chun Chieh Wang, Chao Yung Wang

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

28 Scopus citations


Irisin is an exercise-related myokine. The abundance of irisin is associated with many diseases, such as myocardial infarction, chronic kidney disease, metabolic syndrome, obesity, and diabetes mellitus. In cardiomyocytes, irisin modulates the mitochondrial thermogenesis, regulates ischemic responses, and affects calcium signaling. Previous studies suggested that irisin increases cardiomyoblast mitochondrial functions and protects ischemic and reperfusion injury in ex vivo murine heart. In human, clinical studies have shown that acute myocardial infarction patients with more elevated serum irisin abundances are associated with increased major adverse cardiovascular events. However, the mechanisms responsible for this discrepancy between in myocardial infarction patients and ex vivo murine heart is unclear. Based on the clinical observations, we hypothesized that excessive irisin might lead to mitochondrial dysfunctions and cardiomyocyte damages. Our data showed that overexpression of irisin in mice with the adenovirus resulted in enhanced mitochondrial respiration with a higher oxygen consumption rate. Enhanced irisin expression in heart and irisin treatment in cardiomyocytes increased reactive oxygen species production. Furthermore, irisin treatment in cardiomyocytes enhanced the apoptosis and the cleaved caspase 9 levels in hypoxic condition. Pathway analysis in the murine heart with the overexpression of irisin showed that angiopoietin-Tie2, IL-8, IL-13, TGF-β, and thrombopoietin signaling were affected by irisin. Collectively, these results supported that excessive irisin causes mitochondrial overdrive with a higher reactive oxygen species production, which results in increased apoptosis of cardiomyocytes in a hypoxic environment.

Original languageEnglish
Pages (from-to)2493-2498
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number4
StatePublished - 18 09 2018

Bibliographical note

Publisher Copyright:
© 2018 Elsevier Inc.


  • Apoptosis
  • Irisin
  • Mitochondria
  • Reactive oxygen species


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