Nature Medicine10, 1384 - 1389 (2004)
Published online: 21 November 2004; | doi:10.1038/nm1137
Adiponectin-mediated modulation of hypertrophic signals in the heart
Rei Shibata1, 4, Noriyuki Ouchi1, 4, Masahiro Ito2, Shinji Kihara3, Ichiro Shiojima1, David R Pimentel2, Masahiro Kumada3, Kaori Sato1, Stephan Schiekofer1, Koji Ohashi3, Tohru Funahashi3, Wilson S Colucci2
& Kenneth Walsh1
1
Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street, W611, Boston, Massachusetts 02118, USA.
2
Cardiovascular Medicine Section, Department of Medicine, Boston University Medical Center, and Myocardial Biology Unit, Boston University School of Medicine, 715 Albany Street, X704, Boston, Massachusetts 02118, USA.
3
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, 2-2, Yamada-oka, Suita, Osaka, 565-0871, Japan.
4
These authors equally contributed to this work.
Correspondence should be addressed to Kenneth Walsh kxwalsh@bu.edu
Patients with diabetes and other obesity-linked conditions have increased susceptibility to cardiovascular disorders1. The adipocytokine adiponectin is decreased in patients with obesity-linked diseases2. Here, we found that pressure overload in adiponectin-deficient mice resulted in enhanced concentric cardiac hypertrophy and increased mortality that was associated with increased extracellular signal-regulated kinase (ERK) and diminished AMP-activated protein kinase (AMPK) signaling in the myocardium. Adenovirus-mediated supplemention of adiponectin attenuated cardiac hypertrophy in response to pressure overload in adiponectin-deficient, wild-type and diabetic db/db mice. In cultures of cardiac myocytes, adiponectin activated AMPK and inhibited agonist-stimulated hypertrophy and ERK activation. Transduction with a dominant-negative form of AMPK reversed these effects, suggesting that adiponectin inhibits hypertrophic signaling in the myocardium through activation of AMPK signaling. Adiponectin may have utility for the treatment of hypertrophic cardiomyopathy associated with diabetes and other obesity-related diseases.
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