Exercise Ameliorates Emphysema Of Cigarette Smoke-Induced COPD In Mice Through The Exercise-Irisin-Nrf2 Axis

Int J Chron Obstruct Pulmon Dis. 2019 Nov 14;14:2507-2516. doi: 10.2147/COPD.S226623. eCollection 2019.


Background: Oxidative stress is one of the important mechanisms underlying the pathogenesis of chronic obstructive pulmonary disease (COPD). Irisin is a type of myokine secreted from the muscle during exercise and acts against oxidative stress via nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor with antioxidant properties. Here, we examined the emphysema suppressive effects of the exercise-irisin-Nrf2 axis in mice.

Methods: Mice were divided into three groups, namely, the control, smoking, and exercise + smoking groups. All mice from the smoking and exercise + smoking groups were exposed to cigarette smoke once a day. The mice from the exercise + smoking group were adapted to a treadmill once a day. To investigate the Nrf2 cascade, after 12 weeks, serum irisin concentration and Nrf2 and heme oxygenase-1 (HO-1) expression in the lung homogenate were determined. To evaluate cigarette smoke-induced COPD, the number of inflammatory cells in bronchoalveolar lavage fluid (BALF), mean linear intercept (MLI), and destructive index in the lung tissue were examined.

Results: Serum irisin concentration and the expression levels of Nrf2 and HO-1 in the lung homogenate were significantly higher in mice from the exercise + smoking group than in those from the control and smoking groups. The proportion of neutrophils in the BALF was significantly lower in the exercise + smoking group than in the smoking group. The MLI and destructive index were also significantly smaller in mice from the exercise + smoking group than mice from the smoking group.

Conclusion: Irisin secreted from the muscle during exercise may exert protective effects against oxidative stress via Nrf2 and HO-1, and ameliorate emphysema of cigarette smoke-induced COPD. The exercise-irisin-Nrf2 axis may serve as a novel target for COPD treatment.

Keywords: chronic obstructive pulmonary disease; exercise; heme oxygenase-1; irisin; nuclear factor erythroid 2-related factor 2; oxidative stress.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Exercise Therapy*
  • Fibronectins / blood*
  • Heme Oxygenase-1 / metabolism
  • Lung / metabolism*
  • Lung / physiopathology
  • Male
  • Membrane Proteins / metabolism
  • Mice, Inbred C57BL
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress
  • Pulmonary Disease, Chronic Obstructive / etiology
  • Pulmonary Disease, Chronic Obstructive / metabolism
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Pulmonary Disease, Chronic Obstructive / therapy*
  • Pulmonary Emphysema / etiology
  • Pulmonary Emphysema / metabolism
  • Pulmonary Emphysema / physiopathology
  • Pulmonary Emphysema / prevention & control*
  • Signal Transduction
  • Smoke
  • Tobacco Products*


  • FNDC5 protein, mouse
  • Fibronectins
  • Membrane Proteins
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Smoke
  • Heme Oxygenase-1
  • Hmox1 protein, mouse