Leptin induces elongation of cardiac myocytes and causes eccentric left ventricular dilatation with compensation.
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.
Abe
Yukiko
Y
Department of Cardiovascular Medicine, Kyoto University, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto, 606-8507, Japan.
Ono
Koh
K
Kawamura
Teruhisa
T
Wada
Hiromichi
H
Kita
Toru
T
Shimatsu
Akira
A
Hasegawa
Koji
K
D000818:Animals; D000831:Animals, Newborn; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism* / Q000473:pathology*; D020738:Leptin / Q000008:administration & dosage*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D020738:Leptin