Ursolic acid stimulates mTORC1 signaling after resistance exercise in rat skeletal muscle

A recent study identified ursolic acid (UA) as a potent stimulator of muscle protein anabolism via PI3K/Akt signaling, thereby suggesting that UA can increase Akt-independent mTOR complex 1 (mTORC1) activation induced by resistance exercise via Akt signaling. The purpose of the present study was to investigate the effect of UA on resistance exercise-induced mTORC1 activation. The right gastrocnemius muscle of male Sprague-Dawley rats aged 11 wk was isometrically exercised via percutaneous electrical stimulation (stimulating ten 3-s contractions per set for 5 sets), while the left gastrocnemius muscle served as the control. UA or placebo (PLA; corn oil only) was injected intraperitoneally immediately after exercise. The rats were killed 1 or 6 h after the completion of exercise and the target tissues removed immediately. With placebo injection, the phosphorylation of p70^S6K at Thr389 increased 1 h after resistance exercise but attenuated to the control levels 6 h after the exercise. On the other hand, the augmented phosphorylation of p70^S6K was maintained even 6 h after exercise when UA was injected immediately after exercise. A similar trend of prolonged phosphorylation was observed in PRAS40 Thr²⁴⁶, whereas UA alone or resistance exercise alone did not alter its phosphorylation level at 6 h after intervention. These results indicate that UA is able to sustain resistance exercise-induced mTORC1 activity.