Adipocyte fatty acid-binding protein suppresses cardiomyocyte contraction: a new link between obesity and heart disease.

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.