Telmisartan prevents the glitazone-induced weight gain without interfering with its insulin-sensitizing properties

• Published in: American journal of physiology: endocrinology and metabolism 2007-07, Vol.293 (1), p.E91-E95
• Main Authors: Zanchi, Anne, Dulloo, Abdul G, Perregaux, Christine, Montani, Jean-Pierre, Burnier, Michel
• Format: Article
• Language: English
• Subjects: ACE inhibitors; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; Benzimidazoles - pharmacology; Benzoates - pharmacology; Drug Evaluation, Preclinical; Drug Interactions; Drug therapy; Insulin; Insulin - metabolism; Insulin Resistance; Male; Metabolism; Obesity; Obesity - prevention & control; Rats; Rats, Sprague-Dawley; Rats, Zucker; Rodents; Thiazolidinediones - pharmacology; Weight Gain - drug effects
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00024.2007

1 Division of Nephrology and Department of Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne; and 2 Division of Physiology, University of Fribourg, Fribourg, Switzerland Submitted 11 January 2007 ; accepted in final form 8 March 2007 Glitazones are peroxisome proliferator-activated receptor (PPAR)- agonists with powerful insulin-sensitizing properties. They promote the development of metabolically active adipocytes that can lead to a substantial gain in fat mass. Telmisartan is an ANG II type 1 receptor antagonist with partial PPAR- agonistic properties. Recently, telmisartan has been reported to prevent weight gain and improve insulin sensitivity in diet-induced obese rodents. The goal of this study was to examine the influence of telmisartan on pioglitazone-induced weight gain and insulin-sensitizing properties in the following two models of insulin resistance: a nongenetic model (high-fat-fed Sprague Dawley rats) and the genetically obese fa / fa Zucker rat. After a 4-wk treatment, the pioglitazone-induced increase in fat mass was modest in the Sprague Dawley rats and severe in the Zucker rats. In both models, these effects were substantially decreased by concomitant treatment with telmisartan. The effects of telmisartan on body weight and fat mass in the Zucker rats were abolished by pair feeding, suggesting that it is the result of a decrease in food intake. Telmisartan did not interfere with the insulin-sensitizing properties of pioglitazone. This study demonstrates that telmisartan attenuates the glitazone-induced increase in fat mass without interfering with its insulin-sensitizing properties. glitazones; fat; angiotensin II receptor blocker Address for reprint requests and other correspondence: A. Zanchi, Div. of Nephrology, Rue du Bugnon 17, CHUV, 1011 Lausanne, Switzerland (e-mail: azanchidel{at}hotmail.com )