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

Abstract

Glitazones are peroxisome proliferator-activated receptor (PPAR)-gamma 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-gamma 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.

The Insulin Sparing Effect of Telmisartan in a Case of Type 2 Diabetes Mellitus Associated with Schizophrenia under Treatment of Risperidone

“…As analogous data in an animal experiment, Araki (11,13,14). Different from thiazolidinediones, telmisartan does not induce obesity (13).…”

“…Different from thiazolidinediones, telmisartan does not induce obesity (13). Sugimoto et al (14) (17,18).…”

Selective reduction in body fat mass and plasma leptin induced by angiotensin-converting enzyme inhibition in rats

“…This effect was specifically tested in a recent study that investigated the effect of telmisartan on glitazone-induced weight gain in two models of obesity. 20 They showed that both obese Zucker rats and high-fat fed Sprague-Dawley rats gained more weight when treated with the PPAR-agonist pioglitazone, and that the increases in abdominal and total body fat were substantially decreased by concomitant treatment with telmisartan. This effect of telmisartan was mediated by reduced food intake as pair-fed animals showed a similar reduction in fat mass as animals treated with both pioglitazone and telmisartan.…”

“…In general, studies in rats showed that blockade of the RAS with an AT 1 receptor antagonist reduces body weight gain and visceral or epididymal fat mass. [19][20][21] This effect is usually accompanied by a reduction in food intake, and some studies also suggest that increases in fatty acid metabolism or energy expenditure might be part of the mechanism. However, some AT 1 receptor antagonists were more effective than others, 21 and this difference was attributed to the additional property of some drugs in this class, which are partial agonists at peroxisome proliferator-activated receptor (PPAR)-g. 22 In humans, trials of AT 1 receptor antagonists with low numbers of subjects did not produced significant weight loss, 18,23 but one study reported a significant reduction in visceral fat.…”

Pair feeding-mediated changes in metabolism: stress response and pathophysiology in insulin-resistant, atherosclerosis-prone JCR:LA-cp rats

“…Many putative pharmaceutical agents induce reduced food intake (8,9,36,44), leading to uncertainty as to whether the effects seen were due to direct pharmacological actions of the drugs or were simply secondary effects related to anorexia. A common approach to this problem has been to include control (non-drug-treated) animals in the experimental design that are on a daily basis provided with a single portion of food equal to that consumed by drug-treated animals (so-called pair feeding) (29,57). However, in the course of a pharmaceutical study, in which one of the agents had no effect on food intake, we observed that the pair-fed rats showed significant differences in metabolism and pathophysiology compared with the freely fed control animals.…”