An APPL1-AMPK signaling axis mediates beneficial metabolic effects of adiponectin in the heart

Autor: E. Dale Abel, Kristin Schram, Xiangping Fang, Farah S. L. Thong, Justin H.B. Cresser, Aimin Xu, Rengasamy Palanivel, Riya Ganguly, Gary Sweeney, Joseph Tuinei
Rok vydání: 2010
Předmět:
CD36 Antigens
Male
Carrier Proteins - metabolism
medicine.medical_specialty
Adiponectin - metabolism
Physiology
Endocrinology
Diabetes and Metabolism
CD36
Immunoblotting
Antigens
CD36 - metabolism
Adipokine
Nerve Tissue Proteins
In Vitro Techniques
Biology
Rats
Sprague-Dawley
AMP-activated protein kinase
Physiology (medical)
Internal medicine
medicine
Animals
Immunoprecipitation
Myocytes
Cardiac
RNA
Small Interfering
Adenylate Kinase - metabolism
Beta oxidation
Adaptor Proteins
Signal Transducing
chemistry.chemical_classification
Adiponectin
Myocardium - enzymology - metabolism
Myocardium
Adenylate Kinase
Fatty Acids
AMPK
Fatty acid
Articles
Immunohistochemistry
Rats
Metabolism
Endocrinology
Animals
Newborn
chemistry
biology.protein
Phosphorylation
Receptors
Adiponectin
Carrier Proteins
Signal Transduction
Zdroj: American Journal of Physiology-Endocrinology and Metabolism. 299:E721-E729
ISSN: 1522-1555
0193-1849
DOI: 10.1152/ajpendo.00086.2010
Popis: 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 AMPKα2, 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. Copyright © 2010 the American Physiological Society.
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Databáze: OpenAIRE
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