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Human adipocytes attenuate cardiomyocyte contraction: characterization of an adipocyte-derived negative inotropic activity

Valéria Lamounier-Zepter^*,1, Monika Ehrhart-Bornstein^*, Peter Karczewski, Hannelore Haase, Stefan R. Bornstein^* and Ingo Morano

^* Medical Clinic III, University of Dresden, Dresden, Germany; and

Max-Delbruck-Center for Molecular Medicine, Berlin-Buch, Germany

¹Correspondence: Medical Clinic III, University of Dresden, Fetscherstr. 74, Dresden 01307, Germany. E-mail: Valeria.Zepter{at}uniklinikum-dresden.de

The causal relationship between obesity and heart failure is broadly acknowledged; however, the pathophysiological mechanisms involved remain unclear. In this study we investigated whether human adipocytes secrete cardioactive substances that may affect cardiomyocyte contractility. We cultivated adipocytes obtained from human white adipose tissue and incubated isolated rat adult cardiomyocytes with adipocyte-conditioned or control medium. This is the first report to demonstrate that human adipocytes exhibit cardiodepressant activity with a direct and acute effect on cardiomyocyte contraction. This adipocyte-derived negative inotropic activity directly depresses shortening amplitude as well as intracellular systolic peak Ca²⁺ in cardiomyocytes within a few minutes. The adipocyte-derived cardiodepressant activity was dose-dependent and was completely blunted by heating or by trypsin digestion. Filtration of adipocyte-conditioned medium based on molecular mass characterized the cardiodepressant activity at between 10 and 30 kDa. In summary, adipose tissue exerts highly potent activity with an acute depressant effect directly on cardiomyocytes, which may well contribute to increased heart failure risk in overweight patients—Lamounier-Zepter, V., Ehrhart-Bornstein, M., Karczewski, P., Haase, H., Bornstein, S. R., Morano, I. Human adipocytes attenuate cardiomyocyte contraction: characterization of an adipocyte-derived negative inotropic activity.

Key Words: cardiodepressant activity • calcium transient • obesity • heart failure

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