Chronic neuropeptide Y infusion into the lateral ventricle induces sustained feeding and obesity in mice lacking either Npy1r or Npy5r expression
Chronic neuropeptide Y infusion into the lateral ventricle induces sustained feeding and obesity in mice lacking either Npy1r or Npy5r expression
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DOI：
10.1210/en.2003-0914
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发表时间：
2004-01-01
期刊：
影响因子：
4.8
通讯作者：
Aubert, ML
中科院分区：
文献类型：
--
作者：
Raposinho, PD;Pedrazzini, T;Aubert, ML
神经肽Y(NPY)是一种强大的促食欲素神经递质。NPY的Y1和Y5受体参与调节NPY的食欲刺激活性。为了进一步研究这两种受体在NPY诱导的慢性中枢给药后的高吞噬中的重要性，我们使用了缺乏Npy1r或Npy5r表达的小鼠。将NPY注入野生型小鼠的侧脑室，在7天的时间里刺激了食物的摄取并诱导了肥胖。NPY治疗的小鼠脂肪垫重量以及血浆胰岛素、瘦素和皮质酮水平显著增加。此外，注射NPY可显著降低下丘脑NPY和前阿片黑素皮质素的表达。有趣的是，在基因敲除小鼠中缺乏Npy1r或Npy5r的表达并不影响对慢性NPY注射的这种摄食反应。此外，在这些动物身上出现的肥胖综合症与野生型动物相似。综上所述，这些数据强烈表明，在NPY介导的食物摄入量控制中，Y1和Y5受体信号之间存在生物冗余。
Neuropeptide Y (NPY) is a powerful orexigenic neurotransmitter. The NPY Y1 and Y5 receptors have been implicated in mediating the appetite-stimulating activity of NPY. To further investigate the importance of these two receptors in NPY-induced hyperphagia after chronic central administration, we used mice lacking either Npy1r or Npy5r expression. NPY infusion into the lateral ventricle of wild-type mice stimulated food intake and induced obesity over a 7-d period. Fat pad weight as well as plasma insulin, leptin, and corticosterone levels were strongly increased in NPY-treated mice. In addition, NPY infusion resulted in a significant decrease in hypothalamic NPY and proopiomelanocortin expression. Interestingly, the lack of either Npy1r or Npy5r expression in knockout mice did not affect such feeding response to chronic NPY infusion. Moreover, the obesity syndrome that developed in these animals was similar to that in wild-type animals. Taken together, these data strongly suggest biological redundancies between Y1 and Y5 receptor signaling in the NPY-mediated control of food intake.