Aubert Gregory, Burnier Michel, Dulloo Abdul, Perregaux Christine, Mazzolai Lucia, Pralong François, Zanchi Anne
Service of Endocrinology, Diabetology and Metabolism, Department of Medicine, Lausanne University Hospital, Centre Hospitalier Universitaire Vaudois, Lausanne 1011, Switzerland.
Metabolism. 2010 Jan;59(1):25-32. doi: 10.1016/j.metabol.2009.07.002. Epub 2009 Sep 29.
Telmisartan is an angiotensin II receptor blocker with peroxisome proliferator-activated receptor-gamma 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.
替米沙坦是一种具有过氧化物酶体增殖物激活受体γ激动特性的血管紧张素II受体阻滞剂。在肥胖模型和使用格列酮治疗的啮齿动物中，替米沙坦可防止体重增加并减少食物摄入量。本研究通过检查替米沙坦和吡格列酮对参与食物摄入的神经内分泌介质的影响，进一步探讨它们对体重增加和身体成分的影响及其关联。雄性C57/黑6小鼠喂食高脂饮食，按体重匹配，随机分为4个治疗组：赋形剂组、吡格列酮组、替米沙坦组和吡格列酮-替米沙坦组。分析体重增加、食物和水摄入量、身体成分、血浆瘦素水平以及神经内分泌介质的下丘脑表达。使用厄贝沙坦和血管紧张素II 1(A)受体敲除小鼠进行了额外的研究。替米沙坦消除了赋形剂组和吡格列酮组小鼠的体重和脂肪增加，同时减少了食物摄入量、刺鼠相关蛋白的下丘脑表达以及血浆瘦素水平。神经肽Y和阿黑皮素原的变化与食物摄入量的变化不一致。厄贝沙坦对体重增加和刺鼠相关蛋白表达的影响处于中间水平。替米沙坦对体重增加的影响在血管紧张素II 1(A)受体敲除小鼠中更为明显。本研究证实了替米沙坦对喂食高脂饮食小鼠的厌食作用，并首次表明替米沙坦在调节下丘脑致食性刺鼠相关蛋白方面具有功能作用。这些厌食特性消除了高脂喂养和格列酮治疗小鼠的体重增加和身体成分改变。厌食特性独立于血管紧张素II 1(A)受体。
