gms | German Medical Science

29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

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

23. bis 25.11.2005, Berlin

The Angiotensin-Type1-Receptor Blocker Telmisartan Induces the Hepatic Fatty Acid Oxidation Pathway

Der Angiotensin Typ Rezeptor Blocker Telmisartan Induziert Hepatische Fettsäureoxidation

Meeting Abstract

  • N. Frost - Charité - Universitätsmedizin Berlin, Center for Cardiovascular Research (Berlin, D)
  • M. Clemenz - Charité - Universitätsmedizin Berlin, Center for Cardiovascular Research (Berlin, D)
  • A. Foryst-Ludwig - Charité - Universitätsmedizin Berlin, Center for Cardiovascular Research (Berlin, D)
  • M. Harge - Charité - Universitätsmedizin Berlin, Center for Cardiovascular Research (Berlin, D)
  • T. Unger - Charité - Universitätsmedizin Berlin, Center for Cardiovascular Research (Berlin, D)
  • U. Kintscher - 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. Doc05hochP113

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2005/05hoch113.shtml

Veröffentlicht: 8. August 2006

© 2006 Frost et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Recently it has been demonstrated that a distinct subgroup of Angiotensin-type1-receptor blockers (ARBs), such as Telmisartan and Irbesartan, activate the peroxisome proliferator activated receptor gamma (PPARgamma) as partial agonists. Telmisartan improves insulin sensitivity, hypertriglyceridemia, and prevents weight gain in diet-induced obese animals. To assess the molecular mechanisms of beneficial effects of Telmisartan on dyslipidemia and body weight, we studied the regulation of the hepatic fatty-acid (FA) oxidation pathway by Telmisartan.

FA oxidation genes within the hepatic ß-oxidative pathway were studied by stimulating the human hepatoma cell line HepG2 and the murine cell line AML12 with Telmisartan and WY14.643 an established stimulator of hepatic FA-oxidation. Gene regulation was studied by quantitative real-time PCR. In HepG2 cells Telmisartan induced carnitine-palmitoyl-transferase Ia (CPT1a) gene expression by 2.8+1.9 fold in a concentration of 50 mikromol/Liter M (p<0,01) which was independent from the Angiotensin-type1-receptor. In AML12 cells long chain acyl-CoA synthetase 1 (Acsl-1) showed a 2.4+0.1 fold induction by Telmisartan even at 10?M (p<0,01). In addition, hepatic gene expression was measured in livers from diet-induced obese mice treated with 3mg/kg/d Telmisartan or vehicle for 10 weeks. Consistently with the in-vitro data, Acsl-1 was induced by 4.1+1.6 fold in the Telmisartan group compared to vehicle-treated animals (p<0,01).

Our results demonstrate that Telmisartan activates genes of the hepatic fatty acid oxidation in vitro and in vivo, providing a potential mechanism of its beneficial actions on diet-induced dyslipidemia and body weight gain.