Mechanism of mitochondrial division improving cardiac function in diabetic mice by promoting fatty acid oxidation
10.3969/j.issn.1009-0126.2024.12.020
- VernacularTitle:线粒体分裂通过促进脂肪酸氧化改善糖尿病小鼠心脏功能的机制研究
- Author:
Xiaoyan DING
1
;
Yongqing CHEN
;
Xiaogang SONG
;
Lili LÜ
;
Manman ZHAI
;
Bing WU
Author Information
1. 730000 兰州,解放军联勤保障部队第九四○医院老年科
- Publication Type:Journal Article
- Keywords:
diabetes mellitus;
models,animal;
mitochondrial dynamics;
lipid peroxides;
myocardium
- From:
Chinese Journal of Geriatric Heart Brain and Vessel Diseases
2024;26(12):1477-1482
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism of mitochondrial division regulating myocardi-al fatty acid oxidation in diabetic mice.Methods A total of 16 7-week-old male SPF C57BLKS/J diabetic mice were randomly divided into model group and mitochondrial division inhibitor 1(mdivi-1)intervention group(intervention group),with 8 mice in each group.Another 8 male SPF C57BLKS/J mice of the same age were fed adaptively for 1 week and served as control group.The changes in blood glucose and body mass were monitored in above groups.Echocardiography was conducted to detect LVEF and LVFS1 rate and E/A between early and late ventricular diastole.The pathological changes of myocardial tissue were observed by HE staining.The size,morpholo-gy and quantity of mitochondria were observed by TEM.Western blotting was used to detect the expression of mitochondrial dynamin-related protein 1(Drp1),peroxisome proliferator activated receptor α(PPARα),long chain acyl-CoA synthetase 4(ACSL4),carnitine palmitoyl transferase 1B(CPT1B),and fatty acid oxidation detection kit was conducted to determine the activity of fat-ty acid oxidation.Results Compared with the control group,the model group presented hyper-trophic cardiomyocytes and significantly larger cross-sectional diameter of cardiomyocytes(22.36±2.80 μm vs 12.71±1.78 μm,P＜0.01)than the control group.Mdivi-1 intervention resul-ted in greatly improved myocardial hypertrophy and obviously smaller cross-sectional diameter of cardiomyocytes(13.79±1.39 μm vs 22.36±2.8 μm,P＜0.01)when compared with the model group.The expression level of myocardial mitochondrial Drp1,number of mitochondria per unit area of myocardial tissue and the protein levels of PPARα,ACSL4 and CPT1B in myocardial cyto-plasm were significantly higher,and the average mitochondrial area of myocardial tissue,the ex-pression of PPARα,ACSL4 and CPT1B in myocardial mitochondria,and fatty acid oxidation activ-ity were significantly lower in the model group than the control group(P＜0.01).After mdivi-1 intervention,the expression level of myocardial mitochondrial Drp1,the number of mitochondria per unit area of myocardial tissue and the protein levels of PPARα,ACSL4 and CPT1B in myocar-dial mitochondria were notably lower,and the expression of PPARα,ACSL4 and CPT1B in myo-cardial mitochondria and fatty acid oxidation activity in myocardial tissue were significantly higher when compared with those in the model group(P＜0.05,P＜0.01).Conclusion In diabetic mice,increased myocardial mitochondrial division,decreased translocation of fatty acid oxidation regula-tory protein from cytoplasm to mitochondria,inhibited fatty acid oxidation,and myocardial injury are observed.Mdivi-1 intervention inhibits mitochondrial division,promotes fatty acid oxidation by increasing the translocation of fatty acid oxidation regulatory proteins to mitochondria,and thus improves cardiac function.
