Journal article
An APPL1-AMPK signaling axis mediates beneficial metabolic effects of adiponectin in the heart
American journal of physiology: endocrinology and metabolism, Vol.299(5), pp.E721-E729
11/2010
DOI: 10.1152/ajpendo.00086.2010
PMCID: PMC2980363
PMID: 20739511
Abstract
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.
Details
- Title: Subtitle
- An APPL1-AMPK signaling axis mediates beneficial metabolic effects of adiponectin in the heart
- Creators
- Xiangping Fang - Department of Biology, York University, Toronto, CanadaRengasamy Palanivel - Department of Biology, York University, Toronto, CanadaJustin Cresser - Department of Biology, York University, Toronto, CanadaKristin Schram - Department of Biology, York University, Toronto, CanadaRiya Ganguly - Department of Biology, York University, Toronto, CanadaFarah S. L Thong - Department of Biology, York University, Toronto, CanadaJoseph Tuinei - Division of Endocrinology Metabolism and Diabetes and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, UtahAimin Xu - Departments of Medicine and Pharmacology, University of Hong Kong, Hong Kong, China; andE. Dale Abel - Division of Endocrinology Metabolism and Diabetes and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, UtahGary Sweeney - Department of Biology, York University, Toronto, Canada
- Resource Type
- Journal article
- Publication Details
- American journal of physiology: endocrinology and metabolism, Vol.299(5), pp.E721-E729
- DOI
- 10.1152/ajpendo.00086.2010
- PMID
- 20739511
- PMCID
- PMC2980363
- NLM abbreviation
- Am J Physiol Endocrinol Metab
- ISSN
- 0193-1849
- eISSN
- 1522-1555
- Publisher
- American Physiological Society; Bethesda, MD
- Grant note
- RO1 HL-73167; UO1 HL-087947 / National Institutes of Health
- Language
- English
- Date published
- 11/2010
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984024401102771
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