Effects of high-intensity interval training and semaglutide on cardiac glycophagy and heart function in db/db mice
10.3969/j.issn.1001-1242.2025.07.001
- VernacularTitle:高强度间歇运动联合司美格鲁肽对db/db小鼠心肌糖自噬和心功能的影响
- Author:
Jianting SUN
1
;
Sijie LAI
1
;
Zhenghong KANG
1
Author Information
1. 武汉体育学院,湖北省 武汉市,430079
- Publication Type:Journal Article
- Keywords:
diabetic cardiomyopathy;
high-intensity intermittent exercise;
semaglutide;
glycophagy;
glycogen ac-cumulation;
myocardial protection
- From:
Chinese Journal of Rehabilitation Medicine
2025;40(7):969-979
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the effects of high-intensity interval training(HIIT)and semaglutide on cardiomyopathy and glycophagy in db/db mice.Method:Forty male db/db mice were randomly divided into diabetic control group(DC,n=10),diabetic+exercise group(DE,n=10),diabetic+semaglutide group(DM,n=10)and diabetic+exercise+semaglutide group(EM,n=10).DE mice and EM mice were conducted a 8-week HIIT treadmill protocol,DM mice and EM mice received daily subcutaneous neck injections of semaglutide at 0.05mg/kg.Body weight and fasting blood glucose were measured regularly.Echocardiography was used to detect cardiac function at the end of the intervention.Myocardial morphology was evaluated by H&E staining;The H&E staining was used to observe the myocardial morphological changes;fibrosis by Masson staining;glycogen accumulation by periodic acid-Schiff staining;and cardiomyocyte hypertrophy by wheat germ agglutinin(WGA)staining.The glycophagy was observed by transmission electron microscopy.Western Blot quantified the IRS-1,P-PI3K,PI3K,p-AKT,AKT,p-GSK3β,GSK3β,p-AMPK,AMPK,p-mTOR,mTOR,LC3Ⅱ/Ⅰ,TFEB and GABARAPL1 in myocar-dial tissue.Result:Compared with DC group,HIIT and/or semaglutide intervention reduced body weight and fasting glu-cose,improved cardiac function and myocardial morphology,decreased fibrosis and cardiomyocyte hypertrophy(reduced cross-sectional area,P<0.05),and lowered glycogen accumulation.Autophagosomes and autophagy vac-uoles containing different amounts of glycogen granule were observed by transmission electron microscopy.Compared with DC group,the protein level of p-mTOR/mTOR in DE mice was significantly decreased,and the protein levels of LC3Ⅱ/Ⅰ,TFEB and GABARAPL1 in DE mice were significantly increased(P<0.05).The phosphorylation levels of AKT and GSK3β in DM mice was significantly increased,and the protein level of TFEB and GABARAPL1 in DM mice was significantly increased(P<0.05).The protein levels of IRS-1,LC3Ⅱ/Ⅰ,TFEB and GABAPARAL1 in EM mice significantly increased,the phosphorylation levels of PI3K,AKT,GSK3β and AMPK were significantly increased.The p-mTOR/mTOR ratio of autophagy negative regula-tor in EM mice was decreased(P<0.05).Compared with single treatment group,the AMPK phosphorylation and LC3Ⅱ/Ⅰ protein expression in EM group were significantly increased(P<0.05).Conclusion:HIIT and semaglutide can improve myocardial fibrosis,glycogen accumulation and cardiac func-tion in db/db mice,and the combined intervention group yields the most pronounced effects,which may be re-lated to AMPK/mTOR pathway activation,enhanced cardiac glycophagy,and reduced myocardial injury.
