| Adipocyte fatty acid-binding protein suppresses cardiomyocyte contraction: a new link between obesity and heart disease. | |
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MedLine Citation:
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PMID: 19608978 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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Valéria Lamounier-Zepter; Christiane Look; Julio Alvarez; Torsten Christ; Ursula Ravens; Wolf-Hagen Schunck; Monika Ehrhart-Bornstein; Stefan R Bornstein; Ingo Morano |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-07-16 |
Journal Detail:
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Title: Circulation research Volume: 105 ISSN: 1524-4571 ISO Abbreviation: Circ. Res. Publication Date: 2009 Aug |
Date Detail:
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Created Date: 2009-08-14 Completed Date: 2009-09-22 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0047103 Medline TA: Circ Res Country: United States |
Other Details:
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Languages: eng Pagination: 326-34 Citation Subset: IM |
Affiliation:
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Medical Clinic III, Dresden University of Technology, Fetscherstr. 74, 01307 Dresden, Germany. Valeria.Zepter@uniklinikum-dresden.de |
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| MeSH Terms | |
Descriptor/Qualifier:
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Action Potentials
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drug effects* Adipocytes / secretion Adult Aged Animals Atherosclerosis / metabolism Calcium / metabolism Calcium Signaling / drug effects* Cells, Cultured Diabetes Mellitus, Type 2 / metabolism Dose-Response Relationship, Drug Fatty Acid-Binding Proteins / isolation & purification, pharmacology*, secretion Female Humans Male Metabolic Syndrome X / metabolism Middle Aged Myocardial Contraction / drug effects* Myocytes, Cardiac / metabolism* Obesity / metabolism Rats Rats, Wistar |
| Chemical | |
Reg. No./Substance:
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0/FABP4 protein, human; 0/FABP4 protein, rat; 0/Fatty Acid-Binding Proteins; 7440-70-2/Calcium |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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