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


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.


CONCLUSIONS
We conclude that the release of FABP4 from adipocytes may be involved in the development of cardiac contractile dysfunction of obese subjects.
Lamounier-Zepter
Valéria
V
Medical Clinic III, Dresden University of Technology, Fetscherstr. 74, 01307 Dresden, Germany. Valeria.Zepter@uniklinikum-dresden.de
Look
Christiane
C
Alvarez
Julio
J
Christ
Torsten
T
Ravens
Ursula
U
Schunck
Wolf-Hagen
WH
Ehrhart-Bornstein
Monika
M
Bornstein
Stefan R
SR
Morano
Ingo
I
D000200:Action Potentials / Q000187:drug effects*; D017667:Adipocytes / Q000378:metabolism; D000328:Adult; D000368:Aged; D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D050556:Fatty Acid-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
C493410:FABP4 protein, human; C524662:FABP4 protein, rat; D050556:Fatty Acid-Binding Proteins; D002118:Calcium