Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Int J Obes (Lond). 2012 Jun;36(6):876-9. doi: 10.1038/ijo.2011.137. Epub 2011 Jul 19.
β3-Adrenergic receptors (β3ARs) negatively regulate β-adrenergic signaling via nitric oxide and are dependent on the adipokine leptin for normal expression in adipocytes, thus making β3AR an attractive candidate for cross-talk with leptin in the heart. Accordingly, we tested the hypothesis that cardiac β3AR 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 β3AR 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 β3AR mRNA levels in ob/ob mice. Both β3AR mRNA and function were restored in ob/ob mice after in vivo leptin repletion. We propose that diminished β3AR 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.
β3-肾上腺素能受体（β3AR）通过一氧化氮负向调节β-肾上腺素能信号，并且依赖于脂肪细胞中的瘦素来正常表达，因此β3AR 成为与心脏中瘦素发生交叉对话的有吸引力的候选物。相应地，我们检验了这样一个假设，即心脏β3AR 的表达和功能依赖于瘦素，并且在瘦素缺乏的 ob/ob 小鼠中严重减少。通过分离的心肌细胞生理学研究，我们发现 ob/ob 心肌细胞和用瘦素拮抗剂处理的野生型心肌细胞中的β3AR 功能显著减弱。这一发现得到了定量 PCR 的支持，该研究表明 ob/ob 小鼠中的β3AR mRNA 水平明显降低。体内补充瘦素后，ob/ob 小鼠中的β3AR mRNA 和功能均得到恢复。我们提出，β3AR 信号的减弱可能是解释瘦素对心肌的直接作用的关键因素，并表明这项工作揭示了瘦素在肥胖相关心肌肥大和心力衰竭中的作用的一个关键特征。
