Exercise training increases fibronectin type III domain-containing protein 5 (FNDC5/irisin) via the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)-pathway. The PGC1α pathway induced FNDC5/irisin changes in response to exercise training and ischemic stroke are not entirely understood. We investigated the relation of the PGC-1α/FNDC5/irisin pathway to exercise training and to the pathophysiology of ischemic stroke in paretic muscles of stroke-induced rat models. We induced cerebral ischemia following completion of high-intensity interval training (HIIT) to evaluate PGC1α-pathway biofactors in paretic muscles. To define the underlying molecular mechanisms for improvement in paretic muscles following cerebral ischemia, we evaluated PCG-1α-pathway factors using immunofluorescence tracking and enzyme-linked immunosorbent assay (ELISA) immunoassay. We found that HIIT for 3 weeks produced increased expression and release of PGC-1α-pathway biomarkers in both the serum and paretic muscle of stroke-induced rats. We also found a close relation between the expression of PCG-1α-pathway factors in skeletal muscle and their concentration in blood. We found that PGC-1α-pathway biomarkers cause irisin up-regulation following induction of cerebral ischemia. The reduction in neurofunctional deficits following increased PGC-1α-pathway biomarkers suggests that these factors may act as markers of improvement in paretic muscle healing following cerebral ischemia.
Keywords: Biofactors; PGC1α pathway; cerebral ischemia; exercise; irisin; muscle wasting; paretic muscle; rats; stroke; training.