Effect of Resistance Exercise on Muscle Metabolism and Autophagy in sIBM

Abstract

Purpose: Sporadic inclusion body myositis (sIBM), a muscular degenerative disease in the elderly, is an inflammatory myopathy characterized by muscle weakness in the wrist flexor, quadriceps, and tibialis anterior muscles. We aimed to identify the therapeutic effect of resistance exercise (RE) in improving sIBM symptoms in an sIBM animal model. Methods: Six-week-old male Wistar rats were divided into a sham group (sham, n = 12), chloroquine-control group (CQ-con, n = 12), and chloroquine-RE group (CQ-RE, n = 12). The rats were subjected to 1 wk of exercise adaptation and 8 wk of exercise (three sessions per week). Protein expression was measured by Western blotting. Rimmed vacuoles (RV) were identified by hematoxylin and eosin staining and modified Gomori trichrome staining, and amyloid deposition was examined by Congo red staining. Results: The effects of CQ and RE differed depending on myofiber characteristics. Soleus muscles showed abnormal autophagy in response to CQ, which increased RV generation and amyloid-beta accumulation, resulting in atrophy. RE generated RV and decreased amyloid deposition in soleus muscles and also improved autophagy without generating hypertrophy. This reduced the atrophy signal transduction, resulting in decreased atrophy compared with the CQ-con group. Despite no direct effect of CQ, flexor hallucis longus muscles showed loss of mass because of reduced activity or increased inflammatory response; however, RE increased the hypertrophy signal, resulting in reduced autophagy and atrophy. Conclusions: These results demonstrate that RE had a preventive effect on sIBM induced by CQ treatment in an animal model. However, because the results were from an animal experiment, a more detailed study should be conducted over a longer period, and the effectiveness of different RE programs should also be investigated.