Continuous and Intermittent Exercise Upregulates PGC-1α/ Irisin / BDNF Expression to Improve Obesity-induced Cognitive Impairment in Mice / 中国生物化学与分子生物学报

ABSTRACT

This study aimed to investigate the effects of exercise on prefrontal PGC-1α, Irisin, BDNF, oxidative stress, inflammation, and cognitive function in high-fat diet-induced obese mice, which may provide experimental evidence of exercise rehabilitation methods and target screening for obesity. Three-month-old male C57BL/ 6J wild-type mice were randomly divided into four groups control, high-fat diet, high-fat diet with moderate intensity continuous training, and high-fat diet with high-intensity interval training group, with 10 mice in each group. The mice in the high-fat diet with moderate intensity continuous training group and the high-fat diet with high-intensity interval training group received 8 weeks of moderate-intensity continuous training or high-intensity interval training after 12-week high-fat feeding. Behavioral results showed that compared with the control group, reaction time of adhesive removal test was significantly increased (P<0. 01), and spontaneous alternation rate in Y-maze test and exploration time in the novel object recognition test were significantly decreased (P < 0. 01) in the high-fat diet group, indicating that high-fat diet led to cognitive dysfunction in mice. Results showed that compared with the control group, Nissl bodies dissolution and apoptosis were significantly increased (P<0. 01), levels of PGC-1α, Irisin, BDNF, IL-10, and T-SOD were significantly deceased (P<0. 05, P<0. 01), levels of IL-1β, TNF-α, NF-κB, cleaved Caspase-3, Bax/ Bcl-2, ROS, and MDA were significantly increased in the prefrontal lobe (P<0. 01), indicating that high-fat diet induced excessive inflammation, oxidative stress, and apoptosis, which were conducive to prefrontal lobe damage. Compared with the high-fat diet group, moderate intensity continuous or high-intensity interval training decresed reaction time of adhesive removal test (P<0. 01), increased spontaneous alternation rate of Y-maze test and exploration time of novel object recognition test (P<0. 05, P<0. 01), indicating that both continuous and interval training improved cognitive function in obese mice; meanwhile, Nissl bodies and levels of PGC-1α, Irisin, BDNF, IL-10, and T-SOD were significantly increased (P<0. 05, P<0. 01), and apoptosis and levels of IL-1β, TNF-α, NF-κB, cleaved Caspase-3, Bax/ Bcl-2, ROS, and MDA were significantly reduced in the prefrontal lobe (P<0. 01), indicating that both continuous and interval training alleviated obesity-induced inflammation, oxidative stress, and apoptosis in the prefrontal lobe. Both continuous and interval training significantly upregulated PGC-1α/ Irisin/ BDNF expression in the prefrontal lobe of obese mice, inhibited oxidative stress and inflammation, reduced apoptosis, and resulted in alleviating obesity-induced prefrontal lobe damage and cognitive dysfunction; morevover, interval training better than continuous.