The early metabolic cardiac targets of empagliflozin during the development of heart failure, independent of SGLT2 inhibition - PubMed
3 days ago
- #Heart Failure
- #Empagliflozin
- #Metabolism
- Empagliflozin (EMPA) shows early metabolic cardiac benefits in heart failure (HF) development, independent of SGLT2 inhibition.
- Study methods included inducing HF in mice via TAC/DOCA, followed by metabolic analysis using stable isotope tracers, metabolomics, Western blot, and RNA sequencing.
- EMPA prevented HF by enhancing glycolysis (via GLUT4 and distal glycolysis), reducing harmful metabolic intermediates (malate, glucose-6-P), and increasing ATP levels.
- EMPA activated the ERRα/SIRT3 pathway, boosting mitochondrial energy pathways (TCA cycle, fatty acid metabolism, respiratory chain complexes).
- Key findings: EMPA shifts glucose use without altering glucose/fatty acid oxidation, reduces hypertrophy-driving metabolites, and improves cardiac energy metabolism.