Empagliflozin attenuates elaidic acid-exacerbated cardiac dysfunction post-myocardial infarction via suppression of the NF-κB/NLRP3 pathway

Objective: Myocardial infarction leads to heart failure greatly increasing the risk of adverse cardiovascular events. Empagliflozin (EMPA), a sodium-dependent glucose transporters 2 (SGLT2) inhibitor, has been demonstrated to provide effective cardiovascular protection, while the underlying metabolic mechanisms of EMPA on protecting cardiac dysfunction post-MI remain incompletely clear. The current study was conducted to investigate the metabolic effects of EMPA in hearts with cardiac dysfunction post-MI. Methods: , MI mice were generated and treated with empagliflozin (EMPA) or saline for 4 weeks, assessing cardiac structure and function via ultrasound and histological staining. Concurrently, Fatty acid content in cardiac tissues was evaluated from all three groups using targeted metabolomics, with an assessement of the NF-κB/NLRP3/pyroptosis signaling pathway in each group via western blot and immunohistochemistry. Results: experiments revealed that cardiac structural abnormalities and functional impairment in MI mice were significantly improved by EMPA treatment. Concurrently, EMPA treatment effectively suppressed activation of the NF-κB/NLRP3 signaling pathway, accompanied by reduced levels of IL-1β and IL-18, suggesting decreased levels of cardiomyocyte pyroptosis and markedly alleviated inflammatory infiltration and myocardial fibrosis. Furthermore, targeting lipid metabolism revealed marked accumulation of elaidic acid in cardiomyocytes of MI mice, which was significantly reduced in myocardial tissue following EMPA treatment. This improvement was accompanied by restoration of mitochondrial structure and function. Conclusion: EMPA treatment effectively improves cardiac structure and function in MI mice, potentially through regulating lipid metabolism and reducing tissue EA levels, thereby inhibiting NF-κB/NLRP3/pyroptosis while alleviating mitochondrial structural and functional abnormalities.