GSE193432
Exercise-generated ß-aminoisobutyric acid (BAIBA) reduces cardiomyocytes metabolic stress and apoptosis caused by mitochondrial dysfunction through the miR-208b/AMPK pathway
Objective: To explore the protective effects of exercise-derived ß-aminoisobutyric (BAIBA) on apoptosis and energy metabolism in rats with heart failure. Methods: A rat model of heart failure after myocardial infarction (MI) was started by ligating the left anterior descending branch of the coronary artery, the anterior descending branch of the rats in the SHAM group was only threaded and not ligated. Exercise intervention was given to rats with heart failure. The possible mechanisms by which exercise affected cardiac remodeling after MI were investigated using color ultrasound, HE, Masson, and TUNEL staining, and the detection of apoptosis-associated factors in cardiac tissue. High-throughput sequencing and mass spectrometry were used to measure the production of BAIBA and to explore its protective effects and molecular mechanisms. An in vitro model of apoptosis was created by the application of H2O2 to induce mitochondrial dysfunction. This was then transfected with miR-208b analogue and miR-208b-inhibitor. Apoptosis-related proteins were detected by Western blotting (WB), and ATP production was also assessed. After intervention with BAIBA and compound C, assessments were made of apoptosis, mitochondrial function, lipid uptake, utilization of related proteins, ATP changes, alterations in membrane potential (d?m), and changes in reactive oxygen species (ROS). Results: Compared with the control heart failure (HF) group, exercise improved the function of mitochondria, reversed the expression of apoptosis-related proteins, and increased ATP production. In both the normal and heart failure groups, exercise significantly increased the production of BAIBA. It was shown that BAIBA played a similar role to exercise in ameliorating heart failure. Transcriptome analysis confirmed that the expression of miR-208b was increased after BAIBA intervention, and transfection with miR-208b analogue increased both the expression of apoptosis-related proteins and energy metabolism in H9C2 cells induced by H2O2. Combined analysis of the transcriptome and metabolome identified AMPK as a target for BAIBA to improve metabolic stress. Cell experiments further confirmed that BAIBA increased AMPK phosphorylation and had a protective effect on downstream fatty acid uptake, oxidative efficiency, and mitochondrial function, which could be counteracted by the AMPK inhibitor compound C. Conclusion: Exercise-induced BAIBA can reduce the metabolic stress and apoptosis induced by mitochondrial dysfunction through the miR-208b/AMPK pathway. Overall design: Rats with heart failure, treated with exercise or BAIBA. Examining 3 conditions,each with 3 replicates