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29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Hochdruckliga e. V. DHL ® - Deutsche Hypertonie Gesellschaft Deutsches Kompetenzzentrum Bluthochdruck

23. bis 25.11.2005, Berlin

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Angiotensin Type 1 Receptor Antagonists Induce Human in vitro Adipogenesis by PPARgamma Activation

Angiotensin Rezeptor Blocker aktivieren die in vitro Adipogenese humaner Präadipocyten durch Aktivierung

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  • J. Janke - HELIOS Klinikum Berlin, Franz-Volhard-Klinik (Berlin, D)
  • S. Engeli - HELIOS Klinikum Berlin, Franz-Volhard-Klinik (Berlin, D)
  • M. Schupp - Charité - Universitätsmedizin Berlin, Center for Cardiovascular Research (Berlin, D)
  • K. Gorzelniak - Charité - Universitätsmedizin Berlin, Center for Cardiovascular Research (Berlin, D)
  • F.C. Luft - Charité - Universitätsmedizin Berlin, Center for Cardiovascular Research (Berlin, D)
  • A. Sharma - Charité - Universitätsmedizin Berlin, Center for Cardiovascular Research (Berlin, D)

Hypertonie 2005. 29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Berlin, 23.-25.11.2005. Düsseldorf, Köln: German Medical Science; 2006. Doc05hochP111

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/hoch2005/05hoch111.shtml

Published: August 8, 2006

© 2006 Janke et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Unexpected metabolic effects of RAS-blockade reduced the risk to develop type 2 diabetes mellitus by 22% in large randomized controlled trials. The underlying mechanism of the insulin-sensitizing/anti-diabetic effect of ARBs is not known as yet. Activation of PPARgamma by telmisartan in mouse clonal preadipocytes has recently been described, leading to increased adipogenesis. As newly differentiated small adipocytes are more insulin sensitive than old and large adipocytes, the adipogenic potential of ARBs is clearly of interest. To elucidate the underlying mechanism of the anti-diabetic effect of ARBs in humans, we investigated the activation of PPARgamma by different ARBs in human preadipocytes and adipocytes. In vitro studies revealed PPARgamma-like effects for telmisartan and irbesartan, less strong effects for losartan and no PPARgamma-like effects of eprosartan. These effects included the induction of adipogenesis and the activation of PPARgamma-target genes (adiponectin and lipoprotein lipase)on mRNA and protein levels. Furthermore, transfection assays of isolated human adipocytes demonstrated activation of the luciferase reporter gene by all sartans, the induced activity of PPARgamma was approximal 2-fold with pioglitazone and 1.5-fold with each sartan. The data suggest that ARBs have effects on adipogenesis and PPARgamma-target gene expression in human adipose cells that are independent of the blockade of the adipocyte AT1-receptor, but linked to improved insulin sensitivity.