RATIONALE: Adipocyte fatty acid-binding protein (FABP4) is a member of the intracellular lipid-binding protein family and is predominantly expressed in adipose tissue. Emerging evidence suggests that FABP4 plays a role in some aspects of the metabolic syndrome including the development of type 2 diabetes and atherosclerosis. We have recently reported that secretory products from human adipocytes directly and acutely depressed cardiac contractile function. OBJECTIVE: The purpose of this study was to identify this adipocyte-derived cardiodepressant factor. METHODS AND RESULTS: Through mass spectrometry and immunoblotting, we have identified this cardiodepressant factor as FABP4. FABP4 represents 1.8% to 8.1% of total protein secreted by adipocytes in extracellular medium. FABP4 acutely depressed shortening amplitude as well as intracellular systolic peak Ca(2+) in a dose-dependent manner in isolated rat cardiomyocytes. Heart-specific FABP isoform (FABP3) revealed a similar cardiodepressant effect. The N-terminal amino acids 1 to 20 of FABP4 could be identified as the most effective cardiodepressive domain. We could exclude any effect of FABP4 on action potential duration and L-type Ca(2+) current, suggesting a reduced excitation-contraction gain caused by FABP4 as the main inhibitory mechanism. CONCLUSION: We conclude that the release of FABP4 from adipocytes may be involved in the development of cardiac contractile dysfunction of obese subjects.
RATIONALE: Adipocyte fatty acid-binding protein (FABP4) is a member of the intracellular lipid-binding protein family and is predominantly expressed in adipose tissue. Emerging evidence suggests that FABP4 plays a role in some aspects of the metabolic syndrome including the development of type 2 diabetes and atherosclerosis. We have recently reported that secretory products from human adipocytes directly and acutely depressed cardiac contractile function. OBJECTIVE: The purpose of this study was to identify this adipocyte-derived cardiodepressant factor. METHODS AND RESULTS: Through mass spectrometry and immunoblotting, we have identified this cardiodepressant factor as FABP4. FABP4 represents 1.8% to 8.1% of total protein secreted by adipocytes in extracellular medium. FABP4 acutely depressed shortening amplitude as well as intracellular systolic peak Ca(2+) in a dose-dependent manner in isolated rat cardiomyocytes. Heart-specific FABP isoform (FABP3) revealed a similar cardiodepressant effect. The N-terminal amino acids 1 to 20 of FABP4 could be identified as the most effective cardiodepressive domain. We could exclude any effect of FABP4 on action potential duration and L-type Ca(2+) current, suggesting a reduced excitation-contraction gain caused by FABP4 as the main inhibitory mechanism. CONCLUSION: We conclude that the release of FABP4 from adipocytes may be involved in the development of cardiac contractile dysfunction of obese subjects.
Authors: Luc Djoussé; Traci M Bartz; Joachim H Ix; Susan J Zieman; Joseph A Delaney; Kenneth J Mukamal; John S Gottdiener; David S Siscovick; Jorge R Kizer Journal: Obesity (Silver Spring) Date: 2011-10-20 Impact factor: 5.002
Authors: Luc Djoussé; Traci M Bartz; Joachim H Ix; Jinesh Kochar; Jorge R Kizer; John S Gottdiener; Russell P Tracy; Dariush Mozaffarian; David S Siscovick; Kenneth J Mukamal; Susan J Zieman Journal: Eur J Heart Fail Date: 2012-12-06 Impact factor: 15.534