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Adipocyte fatty acid-binding protein suppresses cardiomyocyte contraction: a new link between obesity and heart disease.
- Source :
-
Circulation research [Circ Res] 2009 Aug 14; Vol. 105 (4), pp. 326-34. Date of Electronic Publication: 2009 Jul 16. - Publication Year :
- 2009
-
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.<br />Objective: The purpose of this study was to identify this adipocyte-derived cardiodepressant factor.<br />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.<br />Conclusion: We conclude that the release of FABP4 from adipocytes may be involved in the development of cardiac contractile dysfunction of obese subjects.
- Subjects :
- Adipocytes metabolism
Adult
Aged
Animals
Atherosclerosis metabolism
Calcium metabolism
Cells, Cultured
Diabetes Mellitus, Type 2 metabolism
Dose-Response Relationship, Drug
Fatty Acid-Binding Proteins isolation & purification
Fatty Acid-Binding Proteins metabolism
Female
Humans
Male
Metabolic Syndrome metabolism
Middle Aged
Obesity metabolism
Rats
Rats, Wistar
Action Potentials drug effects
Calcium Signaling drug effects
Fatty Acid-Binding Proteins pharmacology
Myocardial Contraction drug effects
Myocytes, Cardiac metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4571
- Volume :
- 105
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Circulation research
- Publication Type :
- Academic Journal
- Accession number :
- 19608978
- Full Text :
- https://doi.org/10.1161/CIRCRESAHA.109.200501