Cardioprotective effect of nesfatin-1 against isoproterenol-induced myocardial infarction in rats: Role of the Akt/GSK-3β pathway

- To the best of our knowledge, this is the only in vitro study in literature reporting the protective effects of nesfatin-1 against cardiac I/R injury, and it needs to be confirmed by further in vivo studies.
- The present study was carried out to investigate the effect of nesfatin-1 administration on ISO-induced MI in rats, and to evaluate the role of Akt/GSK-3β signaling pathway as a possible mechanism of its protective effect.
- The findings of the present study suggest that novel anorexigenic adipokine, nesfatin-1, may have a cardioprotective effect against ISO-induced MI in rats through an Akt/GSK-3β-dependent mechanism.
- Both nesfatin-1 treatment, as well as nesfatin-1 pretreatment may limit MI-induced infarct size by reducing myocardial apoptosis and inflammation through an Akt/GSK-3β-dependent mechanism.
- Furthermore, the limiting effect of nesfatin-1 treatment against myocardial injury induced by MI may be a more clinically relevant benefit compared to pretreatment since it is not always possible to pretreat MI cases in clinical practise.
- Hence, nesfatin-1 administration may represent a novel therapeutic approach for MI by preventing myocardial injury which contributes to high mortality rates in human.

The present study was designed to evaluate the cardioprotective effects of nesfatin-1, a novel peptide with anorexigenic properties, in rats with isoproterenol (ISO)-induced myocardial infarction (MI), and to further investigate the role of Akt/GSK-3β signaling pathway in the protective effect of nesfatin-1. To induce MI, ISO was subcutaneously injected into the rats for two consecutive days at a dosage of 85 mg/kg/day. ISO-induced myocardial damage was indicated by elevated levels of cardiac specific troponin-T, enhanced myocardial expression of proinflammatory cytokines (interleukin-1β, interleukin-6 and tumor necrosis factor-α), and increased number of cells with apoptotic and necrotic appearance in the myocardial tissue. Levels of p-Akt/Akt and p-GSK-3β/GSK-3β significantly decreased in heart tissue after ISO-induced MI. However, intraperitoneal administration of nesfatin-1 (10 μg/kg/day) elicited a significant cardioprotective activity by lowering the levels of cardiac troponin-T and proinflammatory cytokines, indicating the protective effect of nesfatin-1 against ISO-induced MI. The biochemical findings were further confirmed by histopathological examination, which was demonstrated by reduced number of apoptotic and necrotic cells. Moreover, expressions of p-Akt/Akt and p-GSK-3β/GSK-3β in the myocardium of MI group rats were significantly increased by nesfatin-1 administration, suggesting that nesfatin-1, which appears to possess anti-apoptotic and anti-inflammatory properties, may confer protection against ISO-induced MI via an Akt/GSK-3β-dependent mechanism.