The Effects Of Exercise On The Expression Of MTOR And Synaptic Plasticity-related Protein In The Hippocampus Of Mice With Insulin Resistance

Objectives:Insulin resistance is an important mechanism of cognitive decline in patients with metabolic diseases.And the PI3K/Akt signaling pathway in the hippocampus plays an important role in the cognitive decline caused by insulin resistance.As a downstream target protein of PI3K/Akt,mTOR can regulate the expression of synaptic plasticity-related protein by regulating the process of protein synthesis and degradation.Therefore,this study explored the effects of aerobic or resistance exercise on the expression of synaptic plasticity-related protein in the hippocampus of mice with insulin resistance and the possible mTOR related mechanism by establishing an mouse model of insulin resistance.Methods:6-week-old male C57BL/6J mice(n=48)were randomly divided into normal control group(C,n = 12)and model of insulin resistance induced by high-fat diet group(HFD,n = 36)after a week of adaptive feeding.The mice were maintained for 12 weeks on either normal diet or high-fat diet respectively.Then according to the GTT and ITT experimental data indicators to determine that the mice model of insulin resistance is successfully established.The mice with insulin resistance were randomly divided into insulin resistance,sedentary group(IR,n = 10),insulin resistance + aerobic exercise group(AE,n = 10),insulin resistance + resistance training(RT,n = 10).Mice in group AE and group RT were performed an 12-week increasing speed treadmill training or increasing load ladder-climbing training after being adapted to the treadmill or ladder for a week.Every group of mice was maintained its original way of feeding during the training period.After the intervention,all of the mice were sacrificed after anesthetized and the hippocampus tissue was collected from the brain on ice to extract hippocampus tissue protein.The expressions of Insulin signaling pathway,mTOR,autophagy and synaptic plasticity-related protein in the hippocampus of mice with insulin resistance were detected by Western blotting.Results: 1.The area under the curve(AUC)of GTT and ITT in group HFD was significantly higher than that in group C(P < 0.05).The model of mice with insulin resistance was successfully established.Then after 12 weeks of aerobic or resistance training intervention,the AUC value of group IR was significantly higher than that of group C(P < 0.01),The AUC value of group AE and group RT was significantly lower than that of group IR(P < 0.05).2.Compared with group C,the phosphorylation level of Akt in the hippocampus of mice in group IR decreased significantly(P < 0.05).Compared with group IR,the phosphorylation level of Akt in the hippocampus of mice in group AE increased significantly(P < 0.05),and the phosphorylation and total protein level of Akt in group RT increased significantly(P<0.05,P<0.01).3.Compared with group C,the expressions of PSD95 and SYN in the hippocampus of mice in group IR decreased significantly(P<0.05).Compared with group IR,the expressions of NMDAR and SYN in the hippocampus of mice in group AE and group RT increased significantly(P<0.05),and the expression of PSD95 in group RT were significantly higher than those in group AE(P<0.05).4.Compared with group C,the total protein level of mTOR in group IR decreased,and the phosphorylation level decreased significantly(P<0.05),and the expression of Raptor decreased.Compared with group IR,the expression of mTOR and Raptor and the phosphorylation level of mTOR in group AE and group RT increased significantly(P<0.05).5.Compared with group C,the expression of P70S6 K in group IR showed no significant change,phosphorylation level showed a downward trend,and the expression of 4EBP significantly increased(P<0.05).Compared with group IR,the expression and phosphorylation levels of P70S6 K and 4EBP in group AE and group RT showed no significant change.6.Compared with group C,Beclin1 and LC3II/LC3 I in group IR showed no significant changes.Compared with group IR,Beclin1 in group AE showed an upward trend,LC3II/LC3 I significantly increased,while Beclin1 in group RT remained unchanged,LC3II/LC3 I increased significantly(P<0.05).Conclusion:Both aerobic and resistance training can effectively improve the activity of PI3K/Akt signal pathway to active mTORC1,thus improve the expressions of NMDAR and SYN in the hippocampus of mice with insulin resistance.