Beneficial effects of leptin treatment in a setting of cardiac dysfunction induced by transverse aortic constriction in mouse

摘要

Key points class="unordered" style="list-style-type:disc" id="tjp12365-list-0001">Leptin, is a 16 kDa pleiotropic peptide not only primarily secreted by adipocytes, but also produced by other tissues, including the heart.Controversy exists regarding the adverse and beneficial effects of leptin on the heartWe analysed the effect of a non‐hypertensive dose of leptin on cardiac function, [Ca²⁺]i 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‐overload by transverse aorta constriction.We find that leptin activates mechanisms that contribute to cardiac dysfunction under physiological conditions. 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.These beneficial effects of leptin involve restoration of action potential duration via normalization of transient outward potassium current and sarcoplasmic reticulum Ca²⁺ content via rescue of control sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase levels and ryanodine receptor function modulation, leading to normalization of Ca²⁺ handling parameters.