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

TitleAn APPL1-AMPK signaling axis mediates beneficial metabolic effects of adiponectin in the heart
Authors
KeywordsAMP-activated protein kinase
Fatty acid
Metabolism
Issue Date2010
PublisherAmerican Physiological Society. The Journal's web site is located at http://ajpendo.physiology.org/
Citation
American Journal Of Physiology - Endocrinology And Metabolism, 2010, v. 299 n. 5, p. E721-E729 How to Cite?
AbstractAdiponectin 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.
Persistent Identifierhttp://hdl.handle.net/10722/139449
ISSN
2015 Impact Factor: 3.825
2015 SCImago Journal Rankings: 2.465
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Heart and Stroke Foundation of Canada
Canadian Diabetes Association
Canadian Institutes of Health Research (CIHR)
National Heart, Lung, and Blood InstituteRO1 HL-73167
UO1 HL-087947
Funding Information:

This work was supported by a grant from the Heart and Stroke Foundation of Canada to G. Sweeney. X. Fang was supported by doctoral studentship awards from the Heart and Stroke Foundation of Canada and the Canadian Diabetes Association and R. Palanivel by a postdoctoral fellowship from the Heart and Stroke Foundation of Canada. K. Schram was supported by a Frederick Banting and Charles Best Canadian Graduate Scholarship from CIHR. G. Sweeney also acknowledges support from the Canadian Institutes of Health Research via a New Investigator Award. E. D. Abel is supported by National Heart, Lung, and Blood Institute Grants RO1 HL-73167 and UO1 HL-087947.

References

 

DC FieldValueLanguage
dc.contributor.authorFang, Xen_HK
dc.contributor.authorPalanivel, Ren_HK
dc.contributor.authorCresser, Jen_HK
dc.contributor.authorSchram, Ken_HK
dc.contributor.authorGanguly, Ren_HK
dc.contributor.authorThong, FSLen_HK
dc.contributor.authorTuinei, Jen_HK
dc.contributor.authorXu, Aen_HK
dc.contributor.authorAbel, EDen_HK
dc.contributor.authorSweeney, Gen_HK
dc.date.accessioned2011-09-23T05:50:04Z-
dc.date.available2011-09-23T05:50:04Z-
dc.date.issued2010en_HK
dc.identifier.citationAmerican Journal Of Physiology - Endocrinology And Metabolism, 2010, v. 299 n. 5, p. E721-E729en_HK
dc.identifier.issn0193-1849en_HK
dc.identifier.urihttp://hdl.handle.net/10722/139449-
dc.description.abstractAdiponectin 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.en_HK
dc.languageengen_US
dc.publisherAmerican Physiological Society. The Journal's web site is located at http://ajpendo.physiology.org/en_HK
dc.relation.ispartofAmerican Journal of Physiology - Endocrinology and Metabolismen_HK
dc.rightsAmerican Journal of Physiology: Endocrinology and Metabolism. Copyright © American Physiological Society.-
dc.subjectAMP-activated protein kinaseen_HK
dc.subjectFatty aciden_HK
dc.subjectMetabolismen_HK
dc.subject.meshAdenylate Kinase - metabolism-
dc.subject.meshAdiponectin - metabolism-
dc.subject.meshAntigens, CD36 - metabolism-
dc.subject.meshCarrier Proteins - metabolism-
dc.subject.meshMyocardium - enzymology - metabolism-
dc.titleAn APPL1-AMPK signaling axis mediates beneficial metabolic effects of adiponectin in the hearten_HK
dc.typeArticleen_HK
dc.identifier.emailXu, A:amxu@hkucc.hku.hken_HK
dc.identifier.authorityXu, A=rp00485en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1152/ajpendo.00086.2010en_HK
dc.identifier.pmid20739511-
dc.identifier.pmcidPMC2980363-
dc.identifier.scopuseid_2-s2.0-78349254663en_HK
dc.identifier.hkuros194035en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78349254663&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume299en_HK
dc.identifier.issue5en_HK
dc.identifier.spageE721en_HK
dc.identifier.epageE729en_HK
dc.identifier.isiWOS:000283665600005-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridFang, X=10642149900en_HK
dc.identifier.scopusauthoridPalanivel, R=8655817100en_HK
dc.identifier.scopusauthoridCresser, J=36496575600en_HK
dc.identifier.scopusauthoridSchram, K=24073704800en_HK
dc.identifier.scopusauthoridGanguly, R=36625125300en_HK
dc.identifier.scopusauthoridThong, FSL=6602243080en_HK
dc.identifier.scopusauthoridTuinei, J=21834819700en_HK
dc.identifier.scopusauthoridXu, A=7202655409en_HK
dc.identifier.scopusauthoridAbel, ED=7202417444en_HK
dc.identifier.scopusauthoridSweeney, G=7102852659en_HK

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