One of the major manifestations of
obesity is an increased production of the adipocyte-derived 16-kDa
peptide leptin, which acts mainly on hypothalamic
leptin receptors.
Leptin receptors are widely distributed in various tissues, including the heart. Whereas increased plasma
leptin levels have been reported in patients with
congestive heart failure, systemic alterations induced by
obesity can affect
cardiac hypertrophy, and the direct effects of
leptin on cardiac structure and function still remain to be determined. We first exposed primary cardiac myocytes from neonatal rats to
leptin for 48 h. This resulted in a significant increase in myocyte long-axis length (P < 0.05 at 50 ng/ml) but not in the short-axis width.
Leptin induced the rapid phosphorylation of STAT3 and its
DNA binding in cardiac myocytes. Administration of a JAK2 inhibitor,
AG-490, completely inhibited all of these effects by
leptin. Furthermore, we examined the effect of continuous infusion of
leptin for 4 wk following
myocardial infarction in mice. Echocardiography demonstrated that left ventricular fractional shortening in the
leptin-infused group (28.4 +/- 2.8%) was significantly higher than that in the PBS-infused group (18.4 +/- 2.2%) following
myocardial infarction. Interestingly, left ventricular diastolic dimension in the
leptin-infused group (4.56 +/- 0.12 mm) was also higher than that in the PBS-infused group (4.13 +/- 0.09 mm). These results demonstrate that
leptin induces the elongation of cardiac myocytes via a JAK/STAT pathway and chronic
leptin infusion causes eccentric dilatation with augmented systolic function after
myocardial infarction.