Cellular Biology Adipocyte Fatty Acid–Binding Protein Suppresses Cardiomyocyte Contraction A New Link Between

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 Ca2 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 Ca2 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. (Circ Res. 2009;105:326-334.