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Adipocyte fatty acid-binding protein suppresses cardiomyocyte contraction: A new link between obesity and heart disease.
Circ. Res. 105, 326-334 (2009)
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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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
ISSN (print) / ISBN 0009-7330
Zeitschrift Circulation Research
Quellenangaben Band: 105, Heft: 4, Seiten: 326-334
Verlag Lippincott Williams & Wilkins
Begutachtungsstatus Peer reviewed
Institut(e) Institute for Pancreatic Beta Cell Research (IPI)