Heart failure & cardiomyopathies
Loss of ATP-Dependent Citrate Lyase Drives Left Ventricular Dysfunction by Metabolic Remodeling
Authors' conclusion
Our findings suggest that ACL plays a pivotal role in cardiac metabolism through regulating lipid synthesis and cardiac function.
Study context
- Population
- Human heart tissue from healthy donors and patients with nonischemic cardiomyopathy; Myh6-Cas9 mice
- Comparison
- Cardiac-specific Acly loss vs intact Acly; NICM vs healthy donor heart tissue
Methodological detailshuman heart tissue, cardiomyocyte-specific CRISPR/Cas9 Acly inactivation in Myh6-Cas9 mice, multi-omics, CardioNet computational modeling
- Human heart tissue
- Cardiomyocyte-specific CRISPR/Cas9 Acly inactivation in Myh6-Cas9 mice
- Multi-omics
- CardioNet computational modeling
Main finding
As reported in the abstract
- Reduced ACL abundance and activity in NICM human hearts, correlating with decreased Krebs cycle intermediates
- Cardiac-specific ACL loss reduces acetyl-CoA synthesis, with increased glucose uptake and oxidation, impaired energy flux, elevated AMP:ATP ratios and LV dysfunction
- Compensatory cardiac lipid remodeling and reduced histone 3 acetylation
- AMPK and PKA activation mediating YAP inhibition through phosphorylation
- Increased IDH1 activity prevents allosteric inhibition of glycolysis from cytosolic citrate accumulation
- AAV9-mediated cardiac Idh1 deletion improved cardiac function and energy provision, reducing YAP phosphorylation and restoring YAP signaling
Original publication
Loss of ATP-Dependent Citrate Lyase Drives Left Ventricular Dysfunction by Metabolic Remodeling. Circulation. Published 20 July 2026. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →