Currie P J, Wilson L M
Department of Psychology, University of Manitoba, Winnipeg, Canada.
Pharmacol Biochem Behav. 1991 Jan;38(1):177-84. doi: 10.1016/0091-3057(91)90607-4.
Hypothalamic noradrenergic mechanisms contribute to altered caloric intake in genetically obese (C57BL/6J, ob/ob) mice. Noradrenergic mechanisms, principally in the paraventricular hypothalamus and of the alpha 2 subtype, have also been implicated in the macronutrient intake regulation of nonpathological models. Accordingly, this study assessed the extent to which clonidine, an alpha 2 agonist, altered macronutrient intake in genetically obese (ob/ob) and lean (C57BL/6J, +/?) mice. Following adaptation to a 6-h feeding regimen, mice were injected intraperitoneally with either clonidine (0.1, 0.5 mg/kg) or 0.15 M NaCl (Experiment 1) or 0.025 mg/kg clonidine or saline (Experiment 2) 30 min prior to simultaneous access to separate sources of carbohydrate, fat, and protein. Clonidine doses of 0.1 mg/kg or greater reduced total energy intake and intake of carbohydrate and fat (p less than 0.005) in all mice (Experiment 1). However, 0.025 mg/kg clonidine selectively increased ingestion of carbohydrate in obese mice by 212% of vehicle-injected values (p less than 0.001) without altering intake in lean mice (Experiment 2). These results implicate an alpha 2 receptor mechanism in genetic obesity.
下丘脑去甲肾上腺素能机制导致遗传性肥胖（C57BL/6J，ob/ob）小鼠的热量摄入改变。去甲肾上腺素能机制主要存在于下丘脑室旁核且属于α2亚型，也与非病理模型的常量营养素摄入调节有关。因此，本研究评估了α2激动剂可乐定对遗传性肥胖（ob/ob）和瘦型（C57BL/6J，+/？）小鼠常量营养素摄入的改变程度。在适应6小时喂食方案后，在小鼠同时获取碳水化合物、脂肪和蛋白质的单独来源前30分钟，腹腔注射可乐定（0.1、0.5毫克/千克）或0.15M氯化钠（实验1），或0.025毫克/千克可乐定或生理盐水（实验2）。0.1毫克/千克或更高剂量的可乐定降低了所有小鼠的总能量摄入以及碳水化合物和脂肪的摄入量（p<0.005）（实验1）。然而，0.025毫克/千克可乐定选择性地使肥胖小鼠的碳水化合物摄入量比注射赋形剂的值增加了212%（p<0.001），而未改变瘦型小鼠的摄入量（实验2）。这些结果表明α2受体机制与遗传性肥胖有关。
