Cardiovascular response, feeding behavior and locomotor activity in mice lacking the NPY Y1 receptor
Cardiovascular response, feeding behavior and locomotor activity in mice lacking the NPY Y1 receptor
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DOI：
10.1038/nm0698-722
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发表时间：
1998-06-01
期刊：
影响因子：
82.9
通讯作者：
Brunner, HR
中科院分区：
文献类型：
--
作者：
Pedrazzini, T;Seydoux, J;Brunner, HR
神经肽Y（NPY）是一种36个氨基酸的神经递质，广泛分布于中枢和外周神经系统（1）。NPY参与各种生理反应，包括心血管稳态（2）和下丘脑对食物摄入的控制（3）。已经描述了至少六种NPY受体亚型（4，5）。由于缺乏选择性拮抗剂，每个受体亚型的具体作用一直难以确定。在这里，我们描述了小鼠缺乏的Y1受体亚型的表达。纯合子突变小鼠表现出完全没有血压反应的NPY，而他们保留正常的反应，其他血管收缩剂。每天的食物摄入量，以及NPY刺激的喂养，只是略有减少，而快速诱导的再喂养显着减少。缺乏NPY Y1受体的成年小鼠的特征是体脂增加，而蛋白质含量没有变化。突变小鼠较高的能量效率可能部分来自于在活动期间测量的较低代谢率，与减少的运动活动相关。这些结果表明，NPY Y1受体在NPY介导的心血管反应中的重要性，并通过中央控制能量消耗的体重调节。此外，这些数据也表明了Y1受体在控制食物摄入方面的作用。
Neuropeptide Y (NPY) is a 36-amino-acid neurotransmitter which is widely distributed throughout the central and peripheral nervous system(1). NPY involvement has been suggested in various physiological responses including cardiovascular homeostasis(2) and the hypothalamic control of food intake(3). At least six subtypes of NPY receptors have been described(4,5). Because of the lack of selective antagonists, the specific role of each receptor subtype has been difficult to establish. Here we describe mice deficient for the expression of the Y1 receptor subtype. Homozygous mutant mice demonstrate a complete absence of blood pressure response to NPY, whereas they retain normal response to other vasoconstrictors. Daily food intake, as well as NPY-stimulated feeding, are only slightly diminished, whereas fast-induced refeeding is markedly reduced. Adult mice lacking the NPY Y1 receptor are characterized by increased body fat with no change in protein content. The higher energetic efficiency of mutant mice might result, in part, from the lower metabolic rate measured during the active period, associated with reduced locomotor activity. These results demonstrate the importance of NPY Y1 receptors in NPY-mediated cardiovascular response and in the regulation of body weight through central control of energy expenditure. In addition, these data are also indicative of a role for the Y1 receptor in the control of food intake.