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(Circulation Research. 2009;105:326.)
© 2009 American Heart Association, Inc.

Cellular Biology

Adipocyte Fatty Acid–Binding Protein Suppresses Cardiomyocyte Contraction

A New Link Between Obesity and Heart Disease

Valéria Lamounier-Zepter, Christiane Look, Julio Alvarez, Torsten Christ, Ursula Ravens, Wolf-Hagen Schunck, Monika Ehrhart-Bornstein, Stefan R. Bornstein, Ingo Morano

From the Medical Clinic III (V.L.-Z., C.L., M.E.-B., S.R.B.), Dresden University of Technology, Germany; Institute of Cardiology (J.A.), La Habana, Cuba; Department of Pharmacology and Toxicology (T.C., U.R.), Dresden University of Technology, Germany; Max-Delbrueck-Center for Molecular Medicine (W.-H.S., I.M.), Berlin-Buch, Germany; and University Medicine Charité (I.M.), Berlin, Germany.

Correspondence to Valéria Lamounier-Zepter, Medical Clinic III, Dresden University of Technology, Fetscherstr. 74, 01307 Dresden, Germany. E-mail Valeria.Zepter{at}uniklinikum-dresden.de

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.

Key Words: FABP4 • heart failure • adipocytes • metabolic syndrome