A murine model of ischemia–reperfusion: the perfusion with leptin promotes the apoptosis-related relocation of mitochondrial proteins Bax and cytochrome c

Abstract Background Leptin exerts both protective and deleterious effects on the heart; the first occurs under hypoxia- or ischemia-associated damage, the second is a pro-hypertrophic factor on cardiomyocytes. Therefore, leptin could represent a link between obesity and cardiovascular diseases. The study aimed to investigate the effect of leptin—the same concentration that is frequently measured in obesity and induces cardiac hypertrophy—on murine hearts following an episode of ischemia–reperfusion; moreover, we evaluated the heart's performance, hypertrophy, and activation of apoptosis. Rat hearts were perfused continuously with or without 3.1 nM leptin for one h before and 1 h after an episode of ischemia. Cardiac performance was evaluated, homogenates and mitochondria were prepared for western blot analysis of cardiac actin, leptin receptor, STAT3, pSTAT3, and apoptosis-related proteins Bax, Bcl-2, cytochrome c, and caspase 3. Results Leptin worsened heart recovery after ischemia (p < 0.05 Control vs IR + Lep of Heart Perform, Fig. 2). Although no hypertrophic response was observed, leptin induced the migration of Bax to the mitochondria and the release of cytochrome c into the cytosol (p < 0.05 Control vs IR + Lep, Fig. 5), essential events in the intrinsic/mitochondrial apoptosis. Conclusions Our results indicate that the presence of leptin for 1 h before and after the ischemic insult reduces heart recovery and amplifies apoptotic signaling through the mitochondrial pathway

Leptin Modifies the Rat Heart Performance Associated with Mitochondrial Dysfunction Independently of Its Prohypertrophic Effects

Background. Functional receptors for leptin were described on the surface of cardiomyocytes, and there was a prohypertrophic effect with high concentrations of the cytokine. Therefore, leptin could be a link between obesity and the prevalence of cardiovascular diseases. On the other hand, a deleterious effect of leptin on mitochondrial performance was described, which was also associated with the evolution of cardiac hypertrophy to heart failure. The goal of our study was to analyze the effect of the exposure of rat hearts to a high concentration of leptin on cardiac and mitochondrial function. Methods. Rat hearts were perfused continuously with or without 3.1 nM leptin for 1, 2, 3, or 4 hours. Homogenates and mitochondria were prepared by centrifugation and analyzed for cardiac actin, STAT3, and pSTAT3 by Western blotting, as well as for mitochondrial oxidative phosphorylation, membrane potential, swelling, calcium transport, and content of oxidized lipids. Results. In our results, leptin induced an increased rate-pressure product as a result of increased heart rate and contraction force, as well oxidative stress. In addition, mitochondrial dysfunction expressed as a loss of membrane potential, decreased ability for calcium transport and retention, faster swelling, and less respiratory control was observed. Conclusions. Our results support the role of leptin as a deleterious factor for cardiac function and indicates that mitochondrial dysfunction could be a trigger for cardiac hypertrophy and failure