Adiponectin-mediated modulation of hypertrophic signals in the heart.
Patients with diabetes and other obesity-linked conditions have increased susceptibility to cardiovascular disorders. The adipocytokine adiponectin is decreased in patients with obesity-linked diseases. 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.
Shibata
Rei
R
Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street, W611, Boston, Massachusetts 02118, USA.
Ouchi
Noriyuki
N
Ito
Masahiro
M
Kihara
Shinji
S
Shiojima
Ichiro
I
Pimentel
David R
DR
Kumada
Masahiro
M
Sato
Kaori
K
Schiekofer
Stephan
S
Ohashi
Koji
K
Funahashi
Tohru
T
Colucci
Wilson S
WS
Walsh
Kenneth
K
D055372:AMP-Activated Protein Kinases; D000256:Adenoviridae; D052242:Adiponectin; D000818:Animals; D001794:Blood Pressure; D015153:Blotting, Western; D006332:Cardiomegaly / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D004452:Echocardiography; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D018014:Gene Transfer Techniques; D006339:Heart Rate; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000172:deficiency / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009097:Multienzyme Complexes / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D052242:Adiponectin; D036341:Intercellular Signaling Peptides and Proteins; D009097:Multienzyme Complexes; D017346:Protein Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D055372:AMP-Activated Protein Kinases