| Item Type: | Article | 
|---|---|
| Title: | Interaction of epoxyeicosatrienoic acids and adipocyte fatty acid-binding protein in the modulation of cardiomyocyte contractility | 
| Creators Name: | Lamounier-Zepter, V., Look, C., Schunck, W.H., Schlottmann, I., Woischwill, C., Bornstein, S.R., Xu, A. and Morano, I. | 
| 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. | 
| Keywords: | Eicosanoids, FABP4, Heart Function, Contractility, Obesity, Animals, Rats | 
| Source: | International Journal of Obesity | 
| ISSN: | 0307-0565 | 
| Publisher: | Nature Publishing Group | 
| Volume: | 39 | 
| Number: | 5 | 
| Page Range: | 755-761 | 
| Date: | May 2015 | 
| Official Publication: | https://doi.org/10.1038/ijo.2014.193 | 
| PubMed: | View item in PubMed | 
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