Abstract Fri114: Cardio-protective effect on myocardial mitochondrial damage with optimal dose leptin administration in the ischemic heart failure rat model

Background: Leptin has emerged as a critical modulator of cardiovascular function, metabolism and structure. Recent research has explored the therapeutic benefits of optimal dose of leptin in the ischemic heart failure (IHF), particularly focusing on its impact on myocardial mitochondrial damage. Aims: This study aims to elucidate the mechanisms and therapeutic potential by which optimal dose leptin can ameliorate myocardial mitochondrial structure and function in IHF rat models. Method: To evaluate the effects of optimal dose leptin on myocardial structure and function in IHF, rats were randomly assigned to one of three groups: control, IHF, and leptin-treated IHF. IHF was induced and confirmed through left anterior descending coronary artery ligation, resulting in decreased systolic function that mimics the clinical scenario of acute myocardial infarction. Following IHF induction, the leptin-treated group received intraperitoneal injections of 1 nM leptin for 7 days. Histomorphology, oxidative phosphorylation system (OXPHOS), mitochondrial dynamics and oxygen consumption capacity were measured to assess the effect of leptin in the IHF model. Results: Echocardiography demonstrated significant improvement in systolic function in the leptin-treated group compared to the untreated group. Electron microscopic images revealed more organized and dense cristae and membranes in the leptin-treated group. Moreover, the expression of PGC-1α, as well as OXPHOS components like NDUFB3 and SDHB, and mitochondrial dynamics proteins such as Mfn1, Mfn2 and Drp1, along with oxygen consumption capacity, were significantly increased in the leptin-treated group compared to untreated group. The increased expression of antioxidant enzymes like MnSOD and reduced levels of Caspase-3 further support the notion of leptin-mediated cardio-protection on in the leptin-treated group. Conclusion: This collective evidence strongly suggests that optimal dose leptin administration can exert protective effects on myocardial mitochondrial structure and function in the context of IHF. This cardio-protective effect of optimal dose leptin hints at the feasibility of translating this therapeutic candidate into clinical applications for treating IHF.