An APPL1-AMPK signaling axis mediates beneficial metabolic effects of
adiponectin in the heart.
Authors Fang X, Palanivel R, Cresser J, Schram K, Ganguly R, Thong FS, Tuinei J, Xu A,
Abel ED, Sweeney G
Submitted By Submitted Externally on 3/4/2015
Status Published
Journal American journal of physiology. Endocrinology and metabolism
Year 2010
Date Published 11/1/2010
Volume : Pages 299 : E721 - E729
PubMed Reference 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 AMPKa2, 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.

Investigators with authorship
E. Dale AbelUniversity of Iowa