Neuroendocrine characterization and anorexigenic effects of telmisartan in diet- and glitazone-induced weight gain

Abstract

Telmisartan is an angiotensin II receptor blocker with peroxisome proliferator-activated receptor-γ agonistic properties. Telmisartan prevents weight gain and decreases food intake in models of obesity and in glitazone-treated rodents. This study further investigates the influence of telmisartan and pioglitazone and their association on weight gain and body composition by examining their influence on neuroendocrine mediators involved in food intake. Male C57/Black 6 mice were fed a high-fat diet, weight matched, and randomized in 4 treatment groups: vehicle, pioglitazone, telmisartan, and pioglitazone-telmisartan. Weight gain, food and water intake, body composition, plasma leptin levels, and the hypothalamic expression of neuroendocrine mediators were analyzed. Additional studies were performed with irbesartan and in angiotensin II 1 A receptor-knockout mice. Telmisartan abolished weight and fat gain in vehicle-and pioglitazone-treated mice while decreasing food intake, the hypothalamic expression of the agouti-related protein, and plasma leptin levels. Modifications in neuropeptide Y and proopiomelanocortin were not consistent with changes in food intake. The effects on weight gain and expression of the agouti-related protein were intermediate with irbesartan. The effects of telmisartan on weight gain were even more pronounced in angiotensin II 1 A receptor-knockout mice. This study confirms the anorexigenic effects of telmisartan in mice fed a high-fat diet and suggests for the first time a functional role of telmisartan on hypothalamic orexigenic agouti-related protein regulation. These anorexigenic properties abolish both weight gain and body composition modifications in fat-fed and glitazone-treated mice. The anorexigenic properties are independent from the angiotensin II 1 A receptor.

Enhanced pan‐peroxisome proliferator‐activated receptor gene and protein expression in adipose tissue of diet‐induced obese mice treated with telmisartan

“…Telmisartan also enhanced PPARα gene and protein expression in WAT, which is associated with hypolipidaemic effects (Aubert et al . ), and can control the expression of enzymes involved in the β‐oxidation of fatty acids (Seok & Cha, ), reducing the adiposity index, as verified in our treated obese mice. Activation of PPARα in WAT is linked to both adipocyte differentiation and fatty acid oxidation, playing an important role in whole‐body energy metabolism (Goto et al .…”

“…At physiological levels, leptin inhibits insulin release from pancreatic β‐cells in the postprandial state, thereby avoiding hyperinsulinaemia and hyperphagia (Aubert et al . ; Le Dréan et al . ).…”

Effects of Pioglitazone and Rosiglitazone on Vascular Function of Mesenteric Resistance Arteries in Rat Genetic Hypertension

“…In the chronically treated rats, glitazones were performing their expected metabolic actions as indicated by the higher weight gain in the pioglitazone and rosiglitazone groups compared to the control group of rats. The PPAR-␥ -agonistic properties of glitazones are normally associated with weight gain through the activation of adipogenesis [20] . Blood pressure was lowered only by rosiglitazone, but not by pioglitazone.…”

The Angiotensin II Type 2 Receptor in Brain Functions: An Update

“…There are some evidences suggesting that Ang II could be implicated in food intake: for example, Ang II suppresses food intake after central infusion [32, 160, 161] while blockade of the AT 1 receptor by telmisartan is associated with a decrease in body weight [162]. Furthermore, both AT 1 and AT 2 receptors are expressed in the hypothalamus, which is implicated in the central regulation of food intake.…”