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

Item Type:Article
Title:Adipocyte fatty acid-binding protein suppresses cardiomyocyte contraction. A new link between obesity and heart disease
Creators Name:Lamounier-Zepter, V., Look, C., Alvarez, J., Christ, T., Ravens, U., Schunck, W.H., Ehrhart-Bornstein, M., Bornstein, S.R. and Morano, I.
Abstract: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.
Keywords:FABP4, Heart Failure, Adipocytes, Metabolic Syndrome, Animals, Rats
Source:Circulation Research
Publisher:American Heart Association
Page Range:326-334
Date:14 August 2009
Official Publication:https://doi.org/10.1161/CIRCRESAHA.109.200501
PubMed:View item in PubMed

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