Exercise And/or Metformin Regulate Mitophagy Levels In Db/db Mice Cardiomyocytes

PURPOSE: Previous studies have shown that exercise and metformin have protective effects on myocarditis and fibrosis induced by early diabetes cardiomyopathy, and its potential mechanism may be related to myocardial mitochondrial autophagy. On this basis, this study investigated the changes in myocardial mitochondrial autophagy levels under exercise and/or metformin intervention. METHODS:8 BKS mice were non diabetes quiet group (group WT), and 32 db/db mice were randomly divided into diabetes quiet group (group C), diabetes exercise group (group E), diabetes metformin group (group M), and diabetes exercise combined with metformin group (group EM). All experimental mice underwent 8 weeks of treadmill training at a speed of 12 m/min. The metformin was given 300 mg/kg metformin by gavage daily. Morphological analysis of mitophagy using electron microscopy and immunofluorescence detection. Mitophagy related protein, Parkin and p62, levels were detected by WB through mitochondrial extracting from cardiac tissue. RESULTS: Compared with the group WT, the number of mitophagy sites (0.36 ± 0.20 vs 2.18 ± 0.33), co-localization sites of LC3 and Tom20 (20.50 ± 3.30 vs 39.47 ± 3.65), Parkin and p62 all significantly increased in group C (1.00 ± 0.26 vs 3.84 ± 0.18; 1.00 ± 0.16 vs 2.10 ± 0.08) (P < 0.05). Compared with group C, the number of mitophagy sites in groups E, M, and EM (2.18 ± 0.33 vs 0.82 ± 0.23, 0.73 ± 0.24, 0.45 ± 0.16) was significantly reduced (P < 0.05). The co-localization points of LC3 and Tom20 were significantly reduced in the M and EM groups (39.47 ± 3.65 vs 36.78 ± 4.47, 18.56 ± 2.01, 23.44 ± 2.51) (P < 0.05); Parkin and p62 were significantly reduced in the E and EM groups (3.84 ± 0.18 vs 2.72 ± 0.13, 4.27 ± 0.16, 2.01 ± 0.13; 2.10 ± 0.08 vs 0.83 ± 0.14, 1.98 ± 0.07, 0.96 ± 0.20) (P < 0.05). CONCLUSIONS: A large amount of mitochondrial autophagy was observed in Group C, indicating that a high glucose environment is a trigger for myocardial cell inflammation and damage. Compared to metformin, exercise intervention can more effectively reduce the production of mitochondrial autophagy in high glucose environment. Supported by: This work was supported by the Higher Education Institutions in Jiangsu Province (24KJA310002), Youth Project of National Natural Science Foundation of China (32000839), Graduate Research and Innovation Projects of Jiangsu Province(KYCX23_2380).