Heart failure & cardiomyopathies
METTL3 Is Essential for Exercise Benefits in Diabetic Cardiomyopathy
Authors' conclusion
These studies reveal an essential role of METTL3 in the cardiac benefits of exercise
Study context
- Population
- Mice with diabetic cardiomyopathy (DiaCM) induced by high-fat diet and streptozotocin; patients with nonischemic primary dilated cardiomyopathy without or with diabetes
- Comparison
- METTL3 knockout vs Wild-type
Methodological detailsmouse models, human cardiac tissue
- Mouse models
- Human cardiac tissue
Main finding
As reported in the abstract
- Cardiac METTL3 protein and m6A downregulated in dilated cardiomyopathy, further downregulated with diabetes
- Cardiac METTL3 and m6A downregulated in DiaCM mice, upregulated by exercise
- Cardiomyocyte METTL3 knockout eliminated cardiac benefits of exercise in DiaCM
- Cardiomyocyte METTL3 overexpression improved systolic and diastolic function in 2 DiaCM mouse models
- Exercise enhanced cardiac METTL3 expression via STAT3
- METTL3 attenuated DiaCM via m6A-dependent YBX1 upregulation and Nrf2 activation
- Cardiomyocyte YBX1 overexpression activated Nrf2, attenuated oxidative stress and improved cardiac function; YBX1 knockdown abolished METTL3 benefit
- Pharmacological METTL3 activation with a small molecule attenuated cardiac dysfunction in DiaCM
Original publication
METTL3 Is Essential for Exercise Benefits in Diabetic Cardiomyopathy. Circulation. Published 13 May 2025. doi:10.
Summarised from the published abstract; every number is checked against it