Liver-specific peroxisome proliferator-activated receptor alpha target gene regulation by the angiotensin type 1 receptor blocker telmisartan

Diabetes
Markus ClemenzUlrich Kintscher

Abstract

The angiotensin type 1 receptor blocker (ARB) and peroxisome proliferator-activated receptor (PPAR) gamma modulator telmisartan has been recently demonstrated to reduce plasma triglycerides in nondiabetic and diabetic hypertensive patients. The present study investigates the molecular mechanisms of telmisartans hypolipidemic actions, in particular its effect on the PPARalpha pathway. RESEARCH DESIGN AND METHODS; Regulation of PPARalpha target genes by telmisartan was studied by real-time PCR and Western immunoblotting in vitro and in vivo in liver/skeletal muscle of mice with diet-induced obesity. Activation of the PPARalpha ligand binding domain (LBD) was investigated using transactivation assays. Telmisartan significantly induced the PPARalpha target genes carnitine palmitoyl transferase 1A (CPT1A) in human HepG2 cells and acyl-CoA synthetase long-chain family member 1 (ACSL1) in murine AML12 cells in the micromolar range. Telmisartan-induced CPT1A stimulation was markedly reduced after small interfering RNA-mediated knockdown of PPARalpha. Telmisartan consistently activated the PPARalpha-LBD as a partial PPARalpha agonist. Despite high in vitro concentrations required for PPARalpha activation, telmisartan (3 mg x kg(-1) x da...Continue Reading

References

Nov 1, 1979·Digestive Diseases and Sciences·J A Cohen, M M Kaplan
Jan 1, 1989·Cardiology·W C Roberts
Apr 29, 1997·Proceedings of the National Academy of Sciences of the United States of America·B M FormanR M Evans
Nov 10, 1998·Circulation·B StaelsJ C Fruchart
Mar 17, 1999·Journal of Human Hypertension·T Yamazaki, Y Yazaki
Nov 30, 2000·Biochemical and Biophysical Research Communications·J SakamotoH Sawada
Jun 11, 2002·Annual Review of Nutrition·Frédéric Picard, Johan Auwerx
Sep 27, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Brent A Neuschwander-TetriBruce R Bacon
Jan 31, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Kittichai PromratJay H Hoofnagle
May 17, 2005·Cardiovascular Diabetology·Cristiana VitaleGiuseppe M C Rosano
Jul 28, 2005·Diabetes·Bart Staels, Jean-Charles Fruchart
Feb 10, 2006·Journal of Hepatology·Ronit Shiri-SverdlovMarten H Hofker
Mar 3, 2006·The Journal of Clinical Investigation·Philippe LefebvreBart Staels
Aug 22, 2006·Metabolism: Clinical and Experimental·Ralf A BenndorfRainer H Böger
Dec 1, 2006·The New England Journal of Medicine·Renata BelfortKenneth Cusi
Mar 14, 2007·Journal of Hypertension·Michio ShimabukuroTakeshi Shimabukuro
May 30, 2007·Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme·T InoueK Node

❮ Previous
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Citations

Jun 15, 2011·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Xizhen XuLing Tu
May 15, 2012·Molecular and Cellular Endocrinology·E Matthew MorrisR Scott Rector
Oct 1, 2010·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Sachiko MatsumotoToshiyuki Miyata
Dec 21, 2012·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Kiyo TakeuchiHiromi Rakugi
May 24, 2012·Current Opinion in Lipidology·Anthony S Wierzbicki, Jude Oben
Jun 30, 2010·International Journal of Clinical Practice·S KaserH Tilg
Apr 28, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Deepa S De SilvaFlora Sam
Dec 2, 2011·Journal of Strength and Conditioning Research·Fabian Sanchis-Gomar, Giuseppe Lippi
Aug 11, 2012·Clinical Drug Investigation·Caroline M Perry
Feb 28, 2009·World Journal of Gastroenterology : WJG·Eugen Florin GeorgescuLiliana Vancica
Oct 12, 2011·Journal of Hypertension·Takashi KajiyaTheodore W Kurtz
May 14, 2008·Expert Opinion on Pharmacotherapy·Teruo Inoue, Koichi Node
Jun 1, 2010·Expert Opinion on Drug Metabolism & Toxicology·Sylvia DeppeRalf A Benndorf
Nov 22, 2008·European Journal of Clinical Investigation·A StorkaM Wolzt
Apr 28, 2009·Journal of Hepatology·Yoshitaka NabeshimaKazuaki Chayama
Jul 23, 2013·The American Journal of Pathology·Jonas SieberAndreas W Jehle
Mar 10, 2015·Life Sciences·Sandra Barbosa-da-SilvaCarlos Alberto Mandarim-de-Lacerda
Apr 14, 2015·Gastroenterology Research and Practice·S GittoP Andreone
Feb 22, 2013·American Journal of Hypertension·Václav ZídekTheodore W Kurtz
Jun 7, 2008·American Journal of Hypertension·Theodore W Kurtz, Michal Pravenec
Apr 11, 2018·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Luciana M A BorémSergio H S Santos
Jan 29, 2013·World Journal of Hepatology·Paschalis Paschos, Konstantinos Tziomalos

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