Overwork damages myocardial energy metabolism homeostasis in mice

CUI Junjie; LAI Ruiyin; CHEN Suheng; QU Shanshan; LIAO Yue; MA Xue; LI Yulan

doi:10.12122/j.issn.1673-4254.2025.12.07

Abstract：Objective To investigate the effect of overwork on myocardial energy metabolism in mice.Methods Thirty-two C57BL/6J mice were randomized equally into a control group and 3 overwork groups with overwork for 2,4,and 6 weeks(W2,W4,and W6 groups,respectively).The mice in overwork groups were subjected to daily forced water standing and restraint.The changes in body weight and general condition of the mice were observed weekly.After successful modeling,the mice were examined for changes in echocardiography,blood glucose/lipid profiles,myocardial pathologies,myocardial TG and ATP levels,and expressions in CD36,GLUT1,CPT1B,PPARα,PFKM,and PKM2 using immunohistochemistry,RT-qPCR or Western blotting.Results The mice with prolonged overwork exhibited reduced activity with hair loss,dull fur,and slowed body weight gain without significant changes in cardiac index or function.Blood glucose levels increased significantly in W2 and W4 groups but decreased in W6 group.Serum TG level increased significantly while TC,HDL,and LDL decreased in W4 and W6 groups.HE staining revealed myocardial swelling,disorganization,and vacuolation in the mouse models.Myocardial TG was elevated in W4 and W6 groups and ATP level decreased in W6 group.The mRNA and protein expressions of CPT1B and PPARα were downregulated in W4 and W6 group,and CD36 expression increased significantly in W4 group.GLUT1 and PFKM/PKM2 expressions decreased obviously in W2 group but increased in W4 and W6 group compared with that in W2 group.Conclusion Short-term overwork causes elevation of blood glucose and suppresses glycolysis in mice,while prolonged overwork reduces glucose,increases TG,impairs fatty acid oxidation,and limits glycolytic compensation to eventually result in myocardial damage,lipid accumulation,and ATP deficiency.