Ding Guoliang, Qin Qianhong, He Nu, Francis-David Sharon C, Hou Jie, Liu Jian, Ricks Ernest, Yang Qinglin
Cardiovascular Research Institute, Morehouse School of Medicine, 720 Westview Dr. SW, Atlanta, GA 30310, USA.
J Mol Cell Cardiol. 2007 Jul;43(1):73-84. doi: 10.1016/j.yjmcc.2007.04.014. Epub 2007 Apr 27.
Adiponectin is a protein hormone involved in maintaining energy homeostasis in metabolically active tissues. It enhances glucose and lipid metabolism via activation of AMP-dependent kinase (AMPK) in skeletal muscle and liver. Energy homeostasis is vital for the heart to work as a pump. In this study, we investigated whether adiponectin and its receptors are expressed in adult ventricular cardiomyocytes. We observed adiponectin transcript and protein in cultured ventricular cardiomyocytes isolated from adult rat, by quantitative real-time PCR, ELISA assays, Western blots, and immunofluorescent staining. In addition, we detected adiponectin receptor (AdipoR1 and AdipoR2) expression in the heart. AdipoR1 was expressed in rat myocardium at a level of approximately 50% of that in skeletal muscle; whereas adipoR2 was expressed at a similar level to that in liver. Rosiglitazone, a Peroxisome proliferator activated receptor gamma (PPARgamma) activator, substantially elevated expression of adiponectin in cultured cardiomyocytes and its secretion into cultured media. Rosiglitazone also increased adipoR1 and adipoR2 expression in cardiomyocytes. Treatment of recombinant globular adiponectin in cultured cardiomyocytes increased fatty acid oxidation and glucose uptake via activation of AMPK, suggesting a role for adiponectin in cardiac energy metabolism. Together, these data establish the existence of a local cardiac-specific adiponectin system that is regulated by PPARgamma. Moreover, these findings indicate a role for adiponectin on normal myocardial energy homeostasis, in part, through the activation of AMPK.
脂联素是一种蛋白质激素,参与维持代谢活跃组织中的能量平衡。它通过激活骨骼肌和肝脏中的AMP依赖激酶(AMPK)来增强葡萄糖和脂质代谢。能量平衡对于心脏作为泵发挥功能至关重要。在本研究中,我们调查了脂联素及其受体在成年心室心肌细胞中是否表达。我们通过定量实时PCR、ELISA检测、蛋白质印迹和免疫荧光染色,在从成年大鼠分离的培养心室心肌细胞中观察到了脂联素转录本和蛋白质。此外,我们检测了心脏中脂联素受体(AdipoR1和AdipoR2)的表达。AdipoR1在大鼠心肌中的表达水平约为骨骼肌中的50%;而AdipoR2的表达水平与肝脏中的相似。罗格列酮是一种过氧化物酶体增殖物激活受体γ(PPARγ)激活剂,可显著提高培养心肌细胞中脂联素的表达及其向培养基中的分泌。罗格列酮还增加了心肌细胞中AdipoR1和AdipoR2的表达。在培养的心肌细胞中用重组球状脂联素处理,通过激活AMPK增加了脂肪酸氧化和葡萄糖摄取,表明脂联素在心脏能量代谢中发挥作用。总之,这些数据证实了存在一个由PPARγ调节的局部心脏特异性脂联素系统。此外,这些发现表明脂联素在正常心肌能量平衡中发挥作用,部分是通过激活AMPK。