Dependence of ß3-adrenergic signaling on the adipokine leptin in cardiac myocytes.

ABSTRACT

ß3-Adrenergic receptors (ß3ARs) negatively regulate ß-adrenergic signaling via nitric oxide and are dependent on the adipokine leptin for normal expression in adipocytes, thus making ß3AR an attractive candidate for cross-talk with leptin in the heart. Accordingly, we tested the hypothesis that cardiac ß3AR expression and function are dependent on leptin and are severely diminished in leptin-deficient ob/ob mice. Using isolated cardiac myocyte physiology studies, we found that ß3AR function was significantly diminished in ob/ob myocytes and in wild-type myocytes treated with leptin antagonist. This finding was supported by quantitative PCR demonstrating markedly decreased ß3AR mRNA levels in ob/ob mice. Both ß3AR mRNA and function were restored in ob/ob mice after in vivo leptin repletion. We propose that diminished ß3AR signaling may be the critical element to explain the direct effects of leptin on the myocardium and suggest that this work reveals a key feature in the role of leptin in obesity-related cardiac hypertrophy and heart failure.