Effects Of Resistance Exercise On Pyroptosis-related Proteins In Hippocampus Of Insulin Resistant Mice

Objective: It is known that pyroptosis is a pro-inflammatory programmed death.When pyroptosis occurs,cells swell and membrane pores appear,accompanied by the release of cell contents,which triggers an inflammatory response.Relevant literature has reported that pyroptosis occurs in peripheral tissues of insulin-resistant mice,but whether pyroptosis occurs in the hippocampus of mice during insulin resistance remains unknown.In this paper,a mouse model of insulin resistance was established by high-fat diet to investigate the changes of pyroptosis-related proteins in the hippocampus of insulin-resistant mice,and to observe the changes of pyroptosis-related proteins in the hippocampus of mice after 12 weeks of resistance training.Methods: Six-week-old male C57 BL / 6J mice were housed in cages,4 per cage.After 1 week of adaptive feeding,the mice were randomly divided into a control group(C,n = 12)and a high-fat diet group(HFD,n = 24).Group C was fed ordinary feed,and HFD group was fed high-fat feed(60% fat,D12492).After 12 weeks of feeding,both group C and HFD group were fasted overnight,and blood was collected from the tail vein the next day for glucose tolerance test and insulin tolerance test.Based on the experimental results,it was determined that the insulin resistance model was successfully established.The mice successfully modeled in the HFD group were randomly divided into the insulin resistance group(IR,n = 10)and the insulin resistance + resistance exercise group(RT,n = 10),and continued to be fed with high-fat diet.After 1 week of adaptive exercise in the RT group,resistance exercise was performed.The exercise program is as follows: mice are subjected to resistance ladder training for 12 weeks.The height of the ladder is 1m,the slope is 85 ° to the ground,and the step interval is 2cm.The initial load-bearing intensity is 30% of the mouse's own body weight,and gradually increases the load.The first 4 weeks increase 10% body weight every week,the fifth week to 80% body weight,and thereafter every 10 weeks to increase 10% body weight.Training 3 days a week,training 3 groups every day,5 times in each group,1minute interval, 2minute intervals in the group,the tail of the mouse is gently stimulated with a brush to complete 15 resistance exercises or stop exercise after exhaustion.After 12 weeks of exercise in the resistance exercise group,all mice were sacrificed after anesthesia,and hippocampus was taken for quantitative protein analysis.Results: 1.Increased expression of pyroptosis-related proteins and inflammatory factors in the hippocampus of insulin-resistant mice Compared with group C,the expression levels of pyroptosis-related proteins GSDMDN/GSDMD and inflammatory factors 1L-1? and 1L-18 in the hippocampus of IR group significantly increased(P < 0.05),and the expression of GSDMD protein increased significantly(P < 0.01).2.Activation of NLRP3 inflammasome in the hippocampus of insulin-resistant mice Compared with group C,the expression of NLRP3,inflammasome proteins NLRP3,ASC,and Caspase-1 in hippocampus of IR group mice increased significantly(P < 0.05).3.decline of AMPK / SIRT1 activity in the hippocampus of insulin-resistant mice the Compared with group C,the expression of SIRT1 protein and p-AMPK / AMPK protein levels in the hippocampus of IR group mice were significantly decreased(P < 0.05),and the expression of NF-?B protein in hippocampus of IR group mice was significantly increased(P < 0.01).4.The expression of pyroptosis-related proteins in insulin-resistant mice was reduced after resistance exercise,and the activation of NLRP3 inflammasome was reduced.Compared with the IR group,the expression levels of NLRP3 inflammasome proteins ASC,Caspase-1,and GSDMD,and the inflammatory factors 1L-1? and 1L-18 in the RT group were significantly reduced(P < 0.05).The GSDMD-N/GSDMD significantly decreased(P < 0.01).5.Enhanced AMPK / SIRT1 activity in hippocampus of insulin resistant mice after resistance exercise Compared with the IR group,the expression of SIRT1 protein and p-AMPK / AMPK protein levels in the RT group increased significantly(P < 0.01),while the expression of NF-?B protein in the RT group decreased significantly(P < 0.05).Conclusion: This study found that pyroptosis and inflammatory response occurred in the hippocampus of insulin-resistant mice.The 12-week resistance exercise can increase the activities of AMPK and SIRT1,inhibit the expression of NF-?B and the activation of NLRP3 inflammasome;thereby reducing the expression of pyroptosisrelated proteins and inflammatory factors,and then regulate the pyroptosis and inflammatory response of cells.Resistance exercise can effectively improve the pyroptosis and inflammatory response in the hippocampus of insulin-resistant mice,thereby promoting the stability of hippocampal structure and function,and providing a new reference for the promotion of brain health by exercise.