Article
The Angiotensin-Type1-Receptor Blocker Telmisartan Induces the Hepatic Fatty Acid Oxidation Pathway
Der Angiotensin Typ Rezeptor Blocker Telmisartan Induziert Hepatische Fettsäureoxidation
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Published: | August 8, 2006 |
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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.