ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 OC6.2

Human adipocytes secrete new cardiodepressant factors: a direct link between obesity and heart failure

Valeria Lamounier-Zepter1, Christiane Look1, Wolf-Hagen Schunk2, Stefan Bornstein1, Monika Ehrhart-Bornstein1 & Ingo Morano2

1University Medical Center, Dresden, Germany; 2Max-Delbrueck-Center for Molecular Medicine, Berlin, Germany.

Obesity has long been recognized as an independent risk factor in heart failure. The mechanisms proposed to explain this correlation include hemodynamic changes secondary to obesity, leading to left ventricular remodeling and systolic dysfunction, and cardiomyocyte apoptosis induced by increased lipid accumulation into cardiomyocytes. Adipose tissue is an endocrine organ that secretes a wide variety of bioactive factors, which seem to mediate communication between adipose tissue and other organs such as muscle, liver, pancreas and brain. In this study, we investigated whether human adipose tissue may directly affect heart contractile function by secreting cardioactive substances. We cultivated adipocytes obtained from human white adipose tissue, and treated isolated rat adult cardiomyocytes in cell culture as well as isolated rat heart in Langendorff system with adipocyte-conditioned or control medium. We observed that human adipocytes release factors that strongly and acutely suppress contraction of electrically paced adult cardiomyocytes by attenuating intracellular Ca2+ levels. These adipocyte-derived cardiodepressant factors could be completely blunted by heating and by trypsin-treatment, indicating the involvement of a protein. Using filtration devices, the cardiodepressant factors could be removed by 10 kDa cutoff filtration, but remained after 30 kDa cutoff filtration, defining the molecular weight of the protein between 10 and 30 kDa. Likewise, isolated rat heart perfused with adipocyte-conditioned medium revealed a reversible strong decrease of force generation and of coronary flow due to contraction of the coronary vessels. In conclusion, our findings revealed a hitherto unknown acute cardiodepressant effect of adipocyte-derived factors directly on cardiomyocytes by suppressing intracellular Ca2+ and indirectly by reducing coronary flow, thus suggesting a direct role of adipose tissue in the pathogenesis of heart failure in obese patients.

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