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However, after the establishment of pressure overload, an increase in leptin levels has protective cardiac effects with respect to rescuing the cellular heart failure phenotype.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These beneficial effects of leptin involve restoration of action potential duration via normalization of transient outward potassium current and sarcoplasmic reticulum Ca<jats:sup>2+<\/jats:sup> content via rescue of control sarcoplasmic\/endoplasmic reticulum Ca<jats:sup>2+<\/jats:sup> ATPase levels and ryanodine receptor function modulation, leading to normalization of Ca<jats:sup>2+<\/jats:sup> handling parameters.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Leptin, is a 16\u00a0kDa pleiotropic peptide not only primary secreted by adipocytes, but also produced by other tissues, including the heart. Evidence indicates that leptin may have either adverse or beneficial effects on the heart. To obtain further insights, in the present study, we analysed the effect of leptin treatment on cardiac function, [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> handling and cellular electrophysiology, which participate in the genesis of pump failure and related arrhythmias, both in control mice and in mice subjected to chronic pressure\u2010overload by transverse aorta constriction (TAC). Three weeks after surgery, animals received either leptin (0.36\u00a0mg\u00a0kg<jats:sup>\u20131<\/jats:sup>\u00a0day<jats:sup>\u20131<\/jats:sup>) or vehicle via osmotic minipumps for 3\u00a0weeks. Echocardiographic measurements showed that, although leptin treatment was deleterious on cardiac function in sham, leptin had a cardioprotective effect following TAC. [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> transient in cardiomyocytes followed similar pattern. Patch clamp experiments showed prolongation of action potential duration (APD) in TAC and leptin\u2010treated sham animals, whereas, following TAC, leptin reduced the APD towards control values. APD variations were associated with decreased transient outward potassium current and Kv4.2 and KChIP2 protein expression. TAC myocytes showed a higher incidence of triggered activities and spontaneous Ca<jats:sup>2+<\/jats:sup> waves. These proarrhythmic manifestations, related to Ca<jats:sup>2+<\/jats:sup>\/calmodulin\u2010dependent protein kinase II and ryanodine receptor phosphorylation, were reduced by leptin. The results of the present study demonstrate that, although leptin treatment was deleterious on cardiac function in control animals, leptin had a cardioprotective effect following TAC, normalizing cardiac function and reducing arrhythmogeneity at the cellular level.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp274030","type":"journal-article","created":{"date-parts":[[2017,4,5]],"date-time":"2017-04-05T15:26:28Z","timestamp":1491405988000},"page":"4227-4243","source":"Crossref","is-referenced-by-count":22,"title":["Beneficial effects of leptin treatment in a setting of cardiac dysfunction induced by transverse aortic constriction in mouse"],"prefix":"10.1113","volume":"595","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5338-7884","authenticated-orcid":false,"given":"Nieves","family":"G\u00f3mez\u2010Hurtado","sequence":"first","affiliation":[{"name":"Departament of Pharmacology School of Medicine Complutense University  Madrid Spain"},{"name":"UMR\u2010S 1180 Inserm Univ. 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