The novel exercise-induced hormone irisin protects against neuronal injury via activation of the Akt and ERK1/2 signaling pathways and contributes to.

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The novel exercise-induced hormone irisin protects against neuronal injury via activation of the Akt and ERK1/2 signaling pathways and contributes to the neuroprotection of physical exercise in cerebral ischemia Dong-Jie Li, Yong-Hua Li, Hong-Bin Yuan, Le-Feng Qu, Pei Wang Metabolism - Clinical and Experimental Volume 68, Pages 31-42 (March 2017) DOI: 10.1016/j.metabol.2016.12.003 Copyright © 2016 Elsevier Inc. Terms and Conditions

Fig. 1 Changes of plasma irisin level and intramuscular irisin precursor FNDC5 expression after cerebral ischemic stroke. (A) Comparison of circulating irisin levels between Sham-operated and MCAO mice at 24h after surgery. *P<0.01. N=6 per group. (B) Comparison of irisin precursor FNDC5 protein expression in skeletal muscle between Sham-operated and MCAO mice at 24h after surgery. *P<0.01. N=6 per group. Metabolism - Clinical and Experimental 2017 68, 31-42DOI: (10.1016/j.metabol.2016.12.003) Copyright © 2016 Elsevier Inc. Terms and Conditions

Fig. 2 Correlations between plasma irisin levels and brain infarction volume, neurological deficit score and plasma pro-inflammatory factors. (A) Correlation between plasma irisin levels and brain infarct volume. (B) Correlations between plasma irisin levels and neurological deficit scores. (C) Correlation between plasma irisin levels and plasma TNF-α levels. (D) Correlation between plasma irisin levels and plasma IL-6 levels. (E) Correlation between plasma irisin levels and plasma IL-1β levels. N=24 in A-E. Metabolism - Clinical and Experimental 2017 68, 31-42DOI: (10.1016/j.metabol.2016.12.003) Copyright © 2016 Elsevier Inc. Terms and Conditions

Fig. 3 Effects of irisin treatment on neuronal injury in MCAO mice. (A) The experimental design for the evaluation of action of irisin in MCAO model. (B) Effect of irisin on brain infarct volume. (C-D) Beam walking test and grip test in MCAO mice. (E) Effect of irisin on the change of body weight. (F) Effect of irisin on the brain edema. *P<0.05 versus sham, #P<0.05 versus vehicle. n=6–8 for each group. Metabolism - Clinical and Experimental 2017 68, 31-42DOI: (10.1016/j.metabol.2016.12.003) Copyright © 2016 Elsevier Inc. Terms and Conditions

Fig. 4 Effects of irisin treatment on post-ischemic neuroinflammation in MCAO mice. (A-B) Immunohistochemistry staining of Iba-1 (A) and MPO-1 (B) in peri-infarct brain tissues of MCAO mice. (C-D) ELISA analyses of TNF-α and IL-6 mRNA expression in peri-infarct brain tissues of MCAO mice. *P<0.05 versus vehicle. n=6–8 for each group. Metabolism - Clinical and Experimental 2017 68, 31-42DOI: (10.1016/j.metabol.2016.12.003) Copyright © 2016 Elsevier Inc. Terms and Conditions

Fig. 5 Effects of irisin treatment on oxidative stress in MCAO mice. (A) Effects of irisin treatment on NO2− Tyr level in peri-infarct brain tissues of MCAO mice. (B) Effects of irisin treatment on superoxide anion level in peri-infarct brain tissues of MCAO mice. (C) Effects of irisin treatment on superoxide anion level in peri-infarct brain tissues of MCAO mice. (D) Effects of irisin treatment on MDA level in peri-infarct brain tissues of MCAO mice. *P<0.05 versus sham, #P<0.05 versus vehicle. n=6–8 for each group. NS, no significance. Metabolism - Clinical and Experimental 2017 68, 31-42DOI: (10.1016/j.metabol.2016.12.003) Copyright © 2016 Elsevier Inc. Terms and Conditions

Fig. 6 Involvement of ERK1/2 and Akt signaling pathways in the neuroprotection of irisin. (A) Immunoblotting analyses showing the phosphorylation of ERK1/2 and Akt signaling pathways by irisin in brain tissues of MCAO mice. *P<0.05 versus vehicle. n=4 for each group. (B-D) Blockade of ERK1/2 and Akt signaling pathways by specific chemical inhibitors partly abolished the beneficial action of irisin on neurological function (B) and neuroinflammation (C-D). *P<0.05 versus blank, #P<0.05 versus irisin treatment. n=6. Metabolism - Clinical and Experimental 2017 68, 31-42DOI: (10.1016/j.metabol.2016.12.003) Copyright © 2016 Elsevier Inc. Terms and Conditions

Fig. 7 Irisin contributes to the neuroprotection of physical exercise against ischemic stroke. (A) The experimental design for the investigation on the role of irisin in the neuroprotection of physical exercise. (B) Effect of administration of irisin neutralizing antibody (irisin NA) on the brain infarct volume. *P<0.05 versus sedentary, #P<0.05 versus control IgG. n=6. (C) Effect of administration of irisin NA on the neurological function. *P<0.05 versus sedentary, #P<0.05 versus control IgG. n=6. (D-E) Effect of administration of irisin NA on the TNF-α (D) and IL-6 (E) mRNA levels. *P<0.05 versus sedentary, #P<0.05 versus control IgG. n=6. Metabolism - Clinical and Experimental 2017 68, 31-42DOI: (10.1016/j.metabol.2016.12.003) Copyright © 2016 Elsevier Inc. Terms and Conditions