Effects of Long-term High-intensity Interval Training on Adiponectin/AMPK Signaling Pathway and Autophagy in Skeletal Muscle of Aged Rats

Objective: To investigate the effects of 8-month high-intensive intervel training (HIIT) and moderate-intensity continuous training (MICT) on adiponectin/AMPK pathway and autophagy in skeletal muscle of aged rats. Methods: 36 female Sprague Dawley rats at 18 months old were selected randomly and divided into three groups: sedentary control (SED) , moderate-intensity continuous training (MICT) , and high-intensity intervel training group (HIIT) , 12 rats per group. HIIT consisted of 9 intervals of 5-minute running on treadmill (1 minutes at 25 m/min and 4 minutes at 15 m/min) , MICT consisted of 45 min of continuous exercise at a moderate intensity (17 m/min) per day, 5 times per week for 8 months, SED group were fed freely but not trained. The body composition was measured by dual-energy X-ray at 48 h after the last training. Handing time, grip strength, maximum running speed, and exhaustion to time were measured 48 h after body composition test. Malonylaldehyde (MDA) and superoxide dismutase 2 (SOD2) levels of gastrocnemius were measured, and levels of 4-hydroxynonenal (4-HNE) , 8-hydroxydeoxyguanosine (8-OHdG) , and insulin-like growth factor 1 (IGF-1) of gastrocnemius were assessed using ELISA. Western blotting was used to evaluate the protein expression of adiponectin, adiponectin receptor 1, sirtuin 3 (SIRT3) , adenosine 5-monophosphate-activated protein kinase (AMPK) , and autophagy (Beclin-1, LC3-I, LC3-II) . Results: Compared with the SED and MICT groups, the percent lean, the percent body fat, and body fat to lean mass ratio of HIIT group were significantly increased. HIIT resulted in a larger improvement in grip strength related to MICT group, with similar increase in inclined plane performance, maximum running speed, and exhaustion to time as compared with the SED group. The protein expression of SOD2 and IGF-1 in the gastrocnemius significantly increased, while the serum IGF-1 levels significantly decreased in both HIIT and MICT groups when compared with the SED group (P < 0.01) . The gastrocnemius and serum levels of 4-HNE and 8-OHdG in the HIIT and MICT groups were lower than those in SED group. Gastrocnemius and serum MDA levels in HIIT group were lower than those in MICT and SED groups (P < 0.01) . HIIT group showed a significant elevation in adiponectin, adiponectin receptor 1, AMPK, and SIRT3 protein content as compared with the SED group. HIIT group experienced higher protein expression of AMPK and adiponectin receptor 1 compared with the MICT group (P<0.05) . Additionally, HIIT group showed a significant elevation of Beclin-1, LC3-I, LC3-II protein expression, and LC3-II/LC3-I ratio compared with the SED group. Correlation analysis showed that exhaustion to time were positive with adiponectin, adiponectin receptor 1, AMPK, and LC3-II/LC3-I ratio, respectively. Conclusions: Long-term high-intensity intervel training upregulate the SOD2 activity may be via IGF-1/SIRT3 axis, preventing skeletal muscle oxidative stress, furthermore, it may also upregulate the autophagic activity by activiting adiponectin/AMPK pathway, attenuating the loss of muscle mass and improving the physical performance in aged rats model.