Endurance exercise boosts Sirtuin 1 and PGC1α in mouse skeletal muscle amid nitric oxide synthesis inhibition

Sarcopenia is an age-related condition characterised by muscle atrophy and loss of muscle mass. The degradation of myofibrils (atrophy) caused by the activation of myofibrillar degradation proteins, e.g. due to a decrease in nitric oxide (NO) associated with aging, contributes to sarcopenia. NO is involved in glucose and lipid metabolism and mitochondrial proliferation; however, whether endurance exercise increases NO production remains unclear. Therefore, in this study, we examined whether endurance exercise promotes metabolic signalling in muscles during continuous suppression of NO production. Mice were assigned to three groups: control, nitric oxide synthase inhibitor administration (L-NAME), and L-NAME administration plus endurance exercise (L-NAME + Ex). The L-NAME group was administered an NO synthesis inhibitor, and the L-NAME + Ex group was administered the inhibitor and performed exercise. The relative amounts of calmodulin (CaM) and nitric oxide synthase (nNOS) in the soleus muscle were significantly increased in the L-NAME + Ex group compared with those in the control and L-NAME groups. In addition, the relative amounts of Sirtuin 1 (Sirt1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) in the L-NAME + Ex group were significantly higher than those in the L-NAME group and similar to those in the control group. CaM and nNOS are involved in NO production, whereas Sirt1 and PGC1α play facilitatory roles in glucose and lipid metabolism. These findings suggest that endurance exercise may enhance muscle metabolic signalling by increasing NO production, even with the suppression of NO synthesis.