Leptin Attenuates Contractile Function in Adult Rat Cardiomyocytes Involved Oxidative Stress and Autophagy

Aim Leptin, a 16 ku hormone from the ob gene, has been identified as an important protein involved obesity. As a chronic metabolic disorder, Obesity is associated with a high risk of developing cardiovascular and metabolic diseases, such as heart failure. The main aim of this paper is to probe the effects of leptin on contractile function of cardiomyocyte in adult rat. And the mechanism of the action involved of oxidative stress and autophagy were investigated. Methods Isolated adult rat cardiomyocytes were exposed to leptin （1, 10, and 100 nmol · L^-1） for 1 hour. The calcium transients and contraction in adult rat cardiomyocytes were recorded with SoftEdge MyoCam system. Using the corresponding agents such as apocynin, tempol and rapamycin, the underlying mecha- nism of leptin involved of oxidative stress and autophagy was determined. Werstern blot was employed to evaluate the expression of LC3B and Beclin-1. Results While perfusing the cardiomyocytes with leptin, peak shortening （PS） and maximal velocity of shortening/relengthening （ ± dL/dtmax） of cell shortening were markedly decreased, and prolonged time to 50% relengthening （TR50%）. As well as, baseline （bl） , peak and time to 50% baseline （TB50%） of calcium transient were markedly depressed. Leptin attenuated autophagy as evidenced by decreased LC3-Ⅱ and Beclin-1. All of the abnormalities were significantly attenuated by apocynin, tempol or rapamyein. Conclusion Leptin has depressing effects on intracellular free calcium and myocardial systolic function. Apocy-nin, tempol or rapamycin could block the effects of leptin. The mechanism involved oxidative stress and autophagy.