Exercise Preconditioning Improved The Mechanism Of Glucose And Lipid Metabolism Disorder Induced By Dexamethasone Injection In Mice

Dexamethasone(Dex) is a synthetic long-acting glucocorticoid,which is widely used in clinical treatment because of the remarkable effects in anti-inflammation and immunosuppression.However,it will also has a series of metabolic side effects while using glucocorticoid to treat and achieve obvious therapeutic effect,such as insulin resistance,dyslipidemia,muscle atrophy,osteoporosis and so on.A new report from Britain showed that more than 1% of the population in the world used glucocorticoid for long-term treatment.Therefore,people pay more and more attention to how to improve metabolic disorders induced by glucocorticoid treatment.Many studies have confirmed that training plays a positive role in promoting body health and preventing diseases.Moderate-intensity aerobic training can prevent and treat metabolic side effects of long-term glucocorticoid use,especially insulin resistance caused by excessive glucocorticoid use.Recent studies have found that high-intensity interval training(HIIT)can improve metabolic disorders caused by glucocorticoids more than traditional moderate-intensity training,but the molecular mechanism is not clear.Therefore,it will help to provide a "precise plan" to improve side effects induced by Dex treatment on whether HIIT can better improve metabolic disorders caused by Dex。Objective :(1)To explore the effect of training preconditioning on glucose and lipid metabolism in Dex mice and its possible mechanism;(2)To explore the effects of different training methods on improving metabolic disorders in Dex mice.Methods: Forty 6-week-old C57BL/6 male mice purchased from the Animal Center of East China Normal University were placed in a clean SPF animal center for rearing(temperature 22±2℃,humidity 50±10%,12 h day and night circulation).After three days of adaptive feeding,mice were randomly divided into four groups.They were: 1)Quiet control group(Con,n=10);2)Dex injection group(DEX,n=10);3)Moderate-intensity training + Dex injection group(MICT,n=10);4)HIIT + Dex injection group(HIIT,n=10).Among them,the mice in the Con group and the DEX group maintained a quiet lifestyle,and the mice in the MICT group underwent moderate-intensity swimming training for 8 weeks.The training program is: the training intervention period is 8 weeks,5 days per week,the first week is adaptive training,and the single swimming training time is 30min;In the second week,the swimming training time increased to 45 min,and the swimming training time from the third week to the eighth week was 60 min.The mice in the HIIT group were trained for 8 weeks with high-intensity intermittent swimming.The training plan was: the training cycle intervention was 8 weeks,and the training was 5 days per week.The intensity of training in the first week was 6% of the load of mice ’own body weight,and the mice rested for 10 s after swimming for 20 s,repeating 10 groups in total;In the second week,the training intensity was 8% of the mouse’s own body weight,and the mice rested for 10 s after swimming for 20 s,repeating 10 groups in total;From the third week to the fourth week,the training intensity was 10% of the mouse’s own body weight,and the mice rested for 10 s after swimming for 20 s,repeating 10 groups in total;From the fifth to the sixth week,the training intensity was 12% of the mouse’s own body weight,and the mice rested for 10 s after swimming for 20 s,repeating 10 groups in total;From the seventh to the eighth week,the training intensity was 12% of the mouse’s own body weight,and the mice rested for 10 s after swimming for 20 s,which was repeated in 12 groups.After 8weeks of training intervention,HIIT group,MICT group and DEX group began to inject Dex intraperitoneally for ten consecutive days,with an injection dose of 0.5 mg/kg.In Con group,normal saline(0.5 mg/kg)was injected intraperitoneally every day for 10 consecutive days.During the period of drug injection,HIIT group and MICT group continued to maintain the original training intervention program.Results:(1)In the whole training intervention process,compared with Con group,there was no significant difference in body weight of mice in DEX group,HIIT group and MICT group.At the injection stage,compared with the Con group,the body weight of mice in the DEX group decreased significantly(P<0.05),and the diet decreased significantly(P<0.05).The body weight of mice in the HIIT group and the MICT group also decreased significantly(P<0.05),and the diet decreased first and then increased,and there was no significant difference overall.(2)In the whole training intervention process,compared with Con group,there was no significant difference in fasting blood glucose FBG in DEX group,HIIT group and MICT group.Compared with Con group,FBG in DEX group increased significantly(P<0.05),but there was no significant difference in FBG between HIIT group and MICT group.(3)Compared with Con group,the area under IPITT curve(P<0.01),serum glucose(P<0.01),serum insulin(P<0.01),and insulin resistance index of DEX group were significantly increased(P<0.01);Serum glucose(P<0.05)and insulin resistance index(P<0.05)of mice in MICT group were significantly increased,but there was no significant difference in area under IPITT curve and serum insulin;The area under IPITT curve of mice in HIIT group increased significantly(P<0.05),and the serum glucose,serum insulin and insulin resistance index were significantly different.Compared with DEX group,the area under IPITT curve(P<0.05),serum glucose(P<0.01),serum insulin(P<0.05),and insulin resistance index(P<0.05)of mice in the MICT group were significantly reduced;the area under IPITT curve(P<0.05),serum glucose(P<0.01),serum insulin(P<0.05),and insulin resistance index(P<0.05)of mice in the HIIT group were significantly reduced.(4)Compared with Con group,serum TC(P<0.01),TG(P<0.01),LDL-C(P<0.01),liver index(P<0.01),groin white fat(P<0.05)and shape factor(P<0.05)of mice in DEX group were significantly increased;The liver index(P<0.05)and brown fat(P<0.05)of mice in the MICT group were significantly increased,but the serum TC,TG,LDL-C,and groin white fat were not significantly different;In HIIT group,LDL-C(P<0.01)and white fat in groin(P<0.05)were significantly increased,while serum TC,TG,liver index,white fat in epididymis and shape factor were not significantly different.Compared with DEX group,serum TC(P<0.01),TG(P<0.01),LDL-C(P<0.01),liver index(P<0.01),groin white fat(P<0.05)in MICT group were significantly increased;serum TC(P<0.01),TG(P<0.01),shape factor(P<0.05),epididymis white fat(P<0.05)in HIIT group were significantly increased.Compared with MICT group,LDL-C of mice in HIIT group was significantly increased,and liver fat deposition index(P<0.01)was significantly decreased.(5)Compared with Con group,the m RNA levels of insulin resistance related genes PI3 K,IRS-1,Akt,APPL1 in DEX group decreased,but there was no significant difference.The m RNA level of lipid metabolism related gene mi R-17-5P increased significantly(P<0.05),and the m RNA levels of CIDEA,FASn,SCD1,ACC1,PGC-1α,AMPK all increased,but there was no significant difference;In MICT group,the m RNA levels of lipid metabolism related gene FASn(P<0.01)decreased significantly,while the m RNA levels of PGC-1 α(P<0.01),AMPK(P<0.05),PPAR α(P<0.01),etc.all increased significantly,and insulin resistance related genes PI3 K,IRS-1,Akt,APPL1 m RNA levels all decreased,but there was no significant difference;The m RNA levels of insulin resistance related genes Akt,lipid metabolism genes AMPK(P<0.01),PGC-1α(P<0.05),PPARα(P<0.01)in HIIT group were significantly increased,and the m RNA levels of CIDEA(P<0.01)and FASn(P<0.01)were significantly decreased.Compared with DEX group,it was found that the m RNA levels of CIDEA(P<0.01)and FASn(P<0.01)in MICT group were significantly decreased,and the m RNA levels of Akt(P<0.05),PGC-1 α(P<0.05),PPAR α(P<0.01)were significantly increased;while the m RNA levels of PI3K(P<0.05),Akt(P<0.05),PGC-1 α(P<0.05),AMPK(P<0.01).(6)Compared with Con group,the protein IRS-1(P<0.05)related to glucose and lipid metabolism in DEX group decreased significantly,and the protein expressions of Akt,FoxO1 and PPAR-α all decreased,but there was no significant difference;The protein expression of IRS-1,Akt,FoxO1 and PPAR-α in MICT group all increased slightly,but there was no significant difference;The protein expressions of IRS-1(P<0.05)and FoxO1(P<0.05)in HIIT group were significantly increased,but the protein expressions of Akt and PPAR-α did not reach significant difference.Compared with DEX group,the protein expressions of IRS-1(P<0.05),Akt(P<0.05),FoxO1(P<0.05)and PPAR-α(P<0.01)were significantly increased,while the protein expressions of IRS-1(P<0.05),AKT(P<0.05),FoxO1(P<0.05)and PPAR-α(P<0.01)in HIIT group were significantly increased.Conclusion:(1)8-week swimming training preconditioning can significantly improve the glucose metabolism disorder induced by glucocorticoid injection,which is manifested by the increase of insulin sensitivity and the improvement of insulin resistance.(2)8-week swimming training preconditioning can significantly improve the lipid metabolism induced by glucocorticoid injection,which is mainly manifested in reducing liver fat accumulation,improving the symptoms of lipid metabolism disorder,and reducing body fat.(3)Compared with moderate-intensity aerobic training,HIIT is more effective in improving insulin resistance and liver lipid metabolism deposition caused by Dex.