Central melanocortin system modulates energy intake and expenditure of obese and lean Zucker rats
Central melanocortin system modulates energy intake and expenditure of obese and lean Zucker rats
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DOI：
10.1152/ajpregu.2001.281.2.r444
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发表时间：
2001-08-01
影响因子：
2.8
通讯作者：
Parker, EM
中科院分区：
文献类型：
--
作者：
Hwa, JJ;Ghibaudi, L;Parker, EM
黑皮质素在食欲和体重调节中发挥着关键作用，因为对该途径的操纵可能导致多种动物模型中肥胖的发生。本研究的目的是使用黑皮质素受体激动剂和拮抗剂来评估黑皮质素在瘦和肥胖 Zucker 大鼠的进食、能量代谢和体重调节中的参与。黑皮质素受体拮抗剂 (SHU9119) 的中枢给药可提高瘦 Zucker 大鼠的食物摄入量和体重，但对肥胖 Zucker 大鼠影响不大。相比之下，黑皮质素受体激动剂 MTII 可以减少瘦大鼠和肥胖大鼠的食物摄入量，但对肥胖 Zucker 大鼠的作用更有效。这些数据表明瘦和肥胖 Zucker 大鼠中均存在功能性黑皮质素受体，但表明肥胖 Zucker 大鼠的内源性黑皮质素张力降低。除了对食物摄入量的影响外，MTII 输注还会在光周期期间增加耗氧量并降低呼吸商，这与剂量有关。我们的数据表明，黑皮质素受体激动剂除了对肥胖和瘦 Zucker 大鼠的食物摄入有抑制作用外，还可以通过增加能量消耗和促进身体脂肪利用来诱导体重减轻。
Melanocortins play a critical role in appetite and body weight regulation, because manipulations of this pathway can lead to the development of obesity in several animal models. The purpose of this study was to use a melanocortin receptor agonist and antagonist to evaluate the involvement of melanocortins in feeding, energy metabolism, and body weight regulation in lean and obese Zucker rats. Central administration of a melanocortin receptor antagonist (SHU9119) elevated food intake and body weight of lean Zucker rats but had little effect in obese Zucker rats. In contrast, the melanocortin receptor agonist MTII reduced food intake in both lean and obese rats but was more potent in the obese Zucker rats. These data indicate the existence of functional melanocortin receptors in both lean and obese Zucker rats but suggest that obese Zucker rats have reduced endogenous melanocortin tone. In addition to its effects on food intake, MTII infusion elevated oxygen consumption and decreased respiratory quotient dose dependently during the light cycle. Our data suggest that a melanocortin receptor agonist can induce weight loss by increasing energy expenditure and promoting body fat utilization in addition to its inhibitory effects on food intake in both obese and lean Zucker rats.