Adiponectin-mediated modulation of hypertrophic signals in the heart

Nat Med. 2004 Dec;10(12):1384-9. doi: 10.1038/nm1137. Epub 2004 Nov 21.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AMP-Activated Protein Kinases
  • Adenoviridae
  • Adiponectin
  • Animals
  • Blood Pressure
  • Blotting, Western
  • Cardiomegaly / drug therapy
  • Cardiomegaly / etiology
  • Cardiomegaly / metabolism*
  • Echocardiography
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Transfer Techniques
  • Heart Rate
  • Immunohistochemistry
  • Intercellular Signaling Peptides and Proteins / deficiency
  • Intercellular Signaling Peptides and Proteins / therapeutic use*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Multienzyme Complexes / metabolism
  • Myocardium / metabolism*
  • Myocytes, Cardiac / metabolism
  • Obesity / complications
  • Obesity / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism
  • Signal Transduction / drug effects*

Substances

  • Adiponectin
  • Intercellular Signaling Peptides and Proteins
  • Multienzyme Complexes
  • Protein-Serine-Threonine Kinases
  • Extracellular Signal-Regulated MAP Kinases
  • AMP-Activated Protein Kinases