Author(s): TOKINOYA, K., KATO, Y., AOKI, K., TAKEKOSHI, K., Institution: YOKOHAMA NATIONAL UNIVERSITY, Country: JAPAN, Abstract-ID: 1745

INTRODUCTION:
Renalase is a secreted cytokine that mediates intercellular communication and contributes to systemic physiological regulation. Although its cardiovascular and metabolic functions have been widely studied, emerging evidence indicates that renalase is responsive to exercise and may participate in skeletal muscle adaptation. Circulating renalase levels increase after exercise training, and previous studies have also reported that skeletal muscle renalase expression is elevated following training, supporting a role for muscle-derived renalase in exercise-induced physiological remodeling. However, whether renalase is required for normal training adaptations in skeletal muscle and whole-body performance remains unclear. Therefore, this study examined the functional significance of renalase during exercise training using renalase knockout mice.
METHODS:
Male Rnls-deficient (KO) and wild-type (WT) mice were assigned to sedentary or treadmill-trained conditions for two months. Training consisted of treadmill running at 25 m/min for 30 min/day, five days per week. Exercise performance, blood lactate, body weight, and transcriptomic profiles of the soleus muscle assessed by RNA sequencing were evaluated to determine physiological and molecular adaptations.
RESULTS:
Exercise training improved performance-related parameters overall; however, renalase deficiency attenuated these training-induced phenotypic adaptations. KO mice showed reduced post-training exercise capacity compared with WT mice despite similar baseline characteristics. Transcriptomic analysis revealed minimal genotype-dependent differences under sedentary conditions, whereas marked differential gene expression appeared after exercise training, indicating that renalase specifically contributes to molecular responses to training rather than basal muscle homeostasis. Differential expression and volcano plot analyses further demonstrated pronounced divergence in transcriptional regulation between WT and KO muscles following training, consistent with impaired adaptive remodeling in the absence of renalase.
CONCLUSION:
These findings indicate that renalase is a key mediator of exercise-induced physiological and transcriptional adaptations in skeletal muscle. The reduced training responsiveness observed in renalase-deficient mice suggests that renalase functions as an exercise-responsive cytokine required for optimal performance improvement and muscle remodeling, highlighting its potential as a molecular target for enhancing training adaptation and metabolic health.