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Interaction of epoxyeicosatrienoic acids and adipocyte fatty acid-binding protein in the modulation of cardiomyocyte contractility

Authors

  • V. Lamounier-Zepter
  • C. Look
  • W.H. Schunck
  • I. Schlottmann
  • C. Woischwill
  • S.R. Bornstein
  • A. Xu
  • I. Morano

Journal

  • International Journal of Obesity

Citation

  • Int J Obes 39 (5): 755-761

Abstract

  • Background: Adipocyte fatty acid-binding protein (FABP4) is a member of a highly conserved family of cytosolic proteins that bind with high affinity to hydrophobic ligands such as saturated and unsaturated long-chain fatty acids and eicosanoids. Recent evidence has supported a novel role for FABP4 in linking obesity with metabolic and cardiovascular disorders. In this context we identified FABP4 as a main bioactive factor released from human adipose tissue that directly suppresses heart contraction in vitro. Since FABP4 is known to be a transport protein, it cannot be excluded that lipid ligands are involved in the cardiodepressant effect as well, acting in an additional and/or synergistic way. Objectives: We investigated a possible involvement of lipid ligands in the negative inotropic effect of adipocyte-factors in vitro. Results: We verified that blocking the CYP epoxygenase pathway in adipocytes attenuates the inhibitory effect of adipocyte-conditioned medium (AM) on isolated adult rat cardiomyocytes, thus suggesting the participation of epoxyeicosatrienoic acids (EETs) in the cardiodepressant activity. Analysis of AM for EETs revealed the presence of 5,6-, 8,9-, 11,12- and 14,15-EET, whereas 5,6-EET represented about 45% of total EET-concentration in AM. Incubation of isolated cardiomyocytes with EETs in similar concentrations as found in AM showed that 5,6-EET directly suppresses cardiomyocyte contractility. Furthermore, after addition of 5,6-EET to FABP4, the negative inotropic effect of FABP4 was strongly potentiated in a concentration-dependent manner. Conclusions: These data suggest that adipocytes release 5,6-EET and FABP4 into the extracellular medium and that the interaction of these factors modulates cardiac function. Therefore, elevated levels of FABP4 and 5,6-EET in obese patients may contribute to the development of heart dysfunction in these subjects.


DOI

doi:10.1038/ijo.2014.193