| An APPL1-AMPK signaling axis mediates beneficial metabolic effects of adiponectin in the heart. | |
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MedLine Citation:
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PMID: 20739511 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Xiangping Fang; Rengasamy Palanivel; Justin Cresser; Kristin Schram; Riya Ganguly; Farah S L Thong; Joseph Tuinei; Aimin Xu; E Dale Abel; Gary Sweeney |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-08-24 |
Journal Detail:
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Title: American journal of physiology. Endocrinology and metabolism Volume: 299 ISSN: 1522-1555 ISO Abbreviation: Am. J. Physiol. Endocrinol. Metab. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-27 Completed Date: 2010-11-16 Revised Date: 2011-11-01 |
Medline Journal Info:
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Nlm Unique ID: 100901226 Medline TA: Am J Physiol Endocrinol Metab Country: United States |
Other Details:
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Languages: eng Pagination: E721-9 Citation Subset: IM |
Affiliation:
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Dept. of Biology, York Univ., Toronto, Ontario, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenylate Kinase
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metabolism* Adiponectin / metabolism* Animals Animals, Newborn Antigens, CD36 / metabolism* Carrier Proteins / metabolism* Fatty Acids / metabolism Immunoblotting Immunohistochemistry Immunoprecipitation Male Myocardium / enzymology, metabolism* Myocytes, Cardiac / enzymology, metabolism Nerve Tissue Proteins / metabolism* RNA, Small Interfering / pharmacology Rats Rats, Sprague-Dawley Receptors, Adiponectin / metabolism Signal Transduction |
| Grant Support | |
ID/Acronym/Agency:
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R01 HL-73167/HL/NHLBI NIH HHS; UO1 HL-087947/HL/NHLBI NIH HHS; //Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/Adiponectin; 0/Antigens, CD36; 0/Appl1 protein, rat; 0/Carrier Proteins; 0/Fatty Acids; 0/Nerve Tissue Proteins; 0/RNA, Small Interfering; 0/Receptors, Adiponectin; 0/adiponectin receptor 1, rat; 0/adiponectin receptor 2, rat; EC 2.7.4.3/Adenylate Kinase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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