Combined effects of high-intensity interval training in the form of swimming exercise and rapamycin-sensitive mTORC1 inhibition on mitochondrial adaptations in mouse skeletal muscles

High-intensity interval training (HIIT) is an effective strategy for enhancing exercise performance by stimulating skeletal muscle mitochondria and increasing their oxidative metabolic capacity. HIIT is also known to stimulate the mechanistic target of rapamycin complex 1 (mTORC1), a key regulatory factor in muscle protein anabolism; however, the role of mTORC1 in HIIT-induced mitochondrial adaptations remains unclear. We hypothesized that mTORC1 modulates mitochondrial adaptation induced by exercise training and investigated the effects of in vivo administration of rapamycin, a canonical inhibitor of mTOR, on skeletal muscle mitochondria after chronic HIIT. Male C57BL6/J mice (n = 21) were evenly assigned to three groups: one group served as the sedentary control (SED), another group performed 4 weeks of HIIT through loaded swimming five times per week (HIIT), and the third group underwent HIIT received intraperitoneal rapamycin administration (HIIT+RAPA). Twenty-four hours after completing the final training session, the animals were anesthetized and euthanized, following which the gastrocnemius, plantaris, and soleus muscles were collected, and their mitochondrial enzyme activities, content, morphology, and regulatory protein levels were evaluated. The combination of HIIT and rapamycin administration increased mitochondrial oxidative phosphorylation (OXPHOS) subunits (P = 0.0363 vs. HIIT, plantaris; P = 0.0176 vs. HIIT, soleus) and decreased the levels of proteins involved in mitochondrial fusion/fission (P = 0.0170 vs. HIIT, gastrocnemius OPA1; P = 0.0140 vs. HIIT, gastrocnemius DRP1 Ser616). Additionally, the number and circularity of mitochondria were increased only in the soleus muscle in the HIIT+RAPA group. These findings indicate that the regulatory role of rapamycin-sensitive mTORC1 on the mitochondrial molecular response and morphological changes in skeletal muscle induced by swimming-type HIIT varies across different skeletal muscles.