Telmisartan suppresses food intake in mice via the melanocortin pathway

Telmisartan, an angiotensin type 1 receptor blocker, is widely used for the treatment of hypertension and related cardiovascular and organ damage. We here describe the effects of telmisartan on food intake and body weight using C57BL/6N mice, KKAy mice that overexpress agouti protein (a mouse model of type 2 diabetes with obesity), and mice deficient for angiotensin II-1a receptor. Telmisartan combined with a high-fat diet significantly reduced food intake and body weight gain in the three groups of mice compared with respective control animals that were fed the high-fat diet without telmisartan. Telmisartan did not induce taste aversion or affect energy expenditure. Intracerebroventricular administration of agouti-related protein, a potent antagonist of the melanocortin 3 receptor (MC3-R) and melanocortin 4 receptor (MC4-R), did not stimulate feeding in telmisartan-treated mice. Telmisartan administration enhanced the alpha-melanocyte stimulating hormone-induced suppression of food intake. This study highlights a potential role for telmisartan in hypothalamic feeding regulation, including melanocortin receptors-mediated suppression of food intake and body weight gain.: