An APPL1-AMPK signaling axis mediates beneficial metabolic effects of adiponectin in the heart
An APPL1-AMPK signaling axis mediates beneficial metabolic effects of adiponectin in the heart
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DOI：
10.1152/ajpendo.00086.2010
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发表时间：
2010-11-01
影响因子：
5.1
通讯作者：
Sweeney, Gary
中科院分区：
文献类型：
--
作者：
Fang, Xiangping;Palanivel, Rengasamy;Sweeney, Gary
[10] Fang X，Palanivel R，Cresser J，Schram K，Ganguly R，Thong FS，Tuinei J，Xu A，Abel艾德，Sweeney G. APPL 1-AMPK信号轴介导脂联素在心脏中的有益代谢作用。Am J Physiol Endocrinol Metab 299：E721-E729，2010.首次发表于2010年8月24日; doi：10.1152/ajpendo.00086.2010.-脂联素通过多种机制促进心脏保护作用，本研究采用原代心肌细胞和离体工作灌流心脏研究脂联素的心脏代谢作用。我们发现，在成年心肌细胞中，脂联素增加CD 36易位和脂肪酸摄取，以及胰岛素刺激的葡萄糖转运和Akt磷酸化。免疫共沉淀显示，脂联素增强了AdipoR 1与APPL 1的结合，随后APPL 1与AMPK α 2的结合，导致ACC的磷酸化和抑制，并增加脂肪酸氧化。使用siRNA有效地敲低新生心肌细胞中的APPL 1，我们证明了APPL 1在介导脂联素增加脂肪酸摄取和氧化中的重要作用。重要的是，在离体工作心脏中也观察到脂肪酸氧化与AMPK和ACC磷酸化的增强。尽管增加脂肪酸氧化和心肌耗氧量，脂联素增加液压功和维持心脏效率。总之，本研究记录了脂联素在心脏中介导的几种有益的代谢作用，并对这些作用背后的机制提供了新的见解，特别是APPL 1的重要性。
Fang X, Palanivel R, Cresser J, Schram K, Ganguly R, Thong FS, Tuinei J, Xu A, Abel ED, Sweeney G. An APPL1-AMPK signaling axis mediates beneficial metabolic effects of adiponectin in the heart. Am J Physiol Endocrinol Metab 299: E721-E729, 2010. First published August 24, 2010; doi: 10.1152/ajpendo.00086.2010.-Adiponectin promotes cardioprotection by various mechanisms, and this study used primary cardiomyocytes and the isolated working perfused heart to investigate cardiometabolic effects. We show in adult cardiomyocytes that adiponectin increased CD36 translocation and fatty acid uptake as well as insulin-stimulated glucose transport and Akt phosphorylation. Coimmunoprecipitation showed that adiponectin enhanced association of AdipoR1 with APPL1, subsequent binding of APPL1 with AMPK alpha 2, which led to phosphorylation and inhibition of ACC and increased fatty acid oxidation. Using siRNA to effectively knockdown APPL1 in neonatal cardiomyocytes, we demonstrated an essential role for APPL1 in mediating increased fatty acid uptake and oxidation by adiponectin. Importantly, enhanced fatty acid oxidation in conjunction with AMPK and ACC phosphorylation was also observed in the isolated working heart. Despite increasing fatty acid oxidation and myocardial oxygen consumption, adiponectin increased hydraulic work and maintained cardiac efficiency. In summary, the present study documents several beneficial metabolic effects mediated by adiponectin in the heart and provides novel insight into the mechanisms behind these effects, in particular the importance of APPL1.