Central and Peripheral Administration of Secretin Inhibits Food Intake in Mice through the Activation of the Melanocortin System
Central and Peripheral Administration of Secretin Inhibits Food Intake in Mice through the Activation of the Melanocortin System
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DOI：
10.1038/npp.2010.178
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发表时间：
2011-01-01
影响因子：
7.6
通讯作者：
Chow, Billy Kwok Chong
中科院分区：
文献类型：
--
作者：
Cheng, Carrie Yuen Yee;Chu, Jessica Yan Shuen;Chow, Billy Kwok Chong
分泌素（Sct）在餐后从十二指肠S细胞释放到循环中。Sct起源于胃肠道系统，其主要功能是延迟胃排空，刺激胰腺和肝脏分泌液体，从而优化消化过程。近年来，Sct及其受体（Sctr）已被确定在下丘脑的离散核团，包括室旁核（PVN）和弓状核（Arc）。这些核团是参与调节身体能量稳态的主要脑部位，从而提供解剖学证据来支持Sct在食欲控制中的功能作用。在这项研究中，使用野生型（wt）、Sct（-/-）和分泌素受体缺陷（Sctr（-/-））小鼠研究了Sct对摄食行为的影响。我们发现，无论是中央和外周给药的Sct可以诱导Fos的表达在PVN和弧，这表明该肽激活下丘脑摄食中心。与这一观点一致，发现Sct增加PVN中促甲状腺激素释放激素和黑皮质素-4受体（Mc 4 r）的转录，并增加阿黑皮素原，但减少Arc中刺豚鼠相关蛋白mRNA的表达。注射Sct能够抑制wt小鼠的食物摄入，但不能抑制Sctr（-/-）小鼠的食物摄入，并且这种作用在用Mc 4 r的拮抗剂SHU 9119预处理后被消除。总之，我们的数据首次表明，Sct是一种厌食肽，并且这种功能是由黑皮质素系统介导的。Neuropsychopharmacology（2011）36，459-471; doi：10.1038/npp.2010.178; 2010年10月6日在线发表
Secretin (Sct) is released into the circulation postprandially from the duodenal S-cells. The major functions of Sct originated from the gastrointestinal system are to delay gastric emptying, stimulate fluid secretion from pancreas and liver, and hence optimize the digestion process. In recent years, Sct and its receptor (Sctr) have been identified in discrete nuclei of the hypothalamus, including the paraventricular nucleus (PVN) and the arcuate nucleus (Arc). These nuclei are the primary brain sites that are engaged in regulating body energy homeostasis, thus providing anatomical evidence to support a functional role of Sct in appetite control. In this study, the effect of Sct on feeding behavior was investigated using wild-type (wt), Sct(-/-), and secretin receptor-deficient (Sctr(-/-)) mice. We found that both central and peripheral administration of Sct could induce Fos expression in the PVN and Arc, suggesting the activation of hypothalamic feeding centers by this peptide. Consistent with this notion, Sct was found to increase thyrotropin-releasing hormone and melanocortin-4 receptor (Mc4r) transcripts in the PVN, and augment proopiomelanocortin, but reduces agouti-related protein mRNA expression in the Arc. Injection of Sct was able to suppress food intake in wt mice, but not in Sctr(-/-) mice, and that this effect was abolished upon pretreatment with SHU9119, an antagonist for Mc4r. In summary, our data suggest for the first time that Sct is an anorectic peptide, and that this function is mediated by the melanocortin system. Neuropsychopharmacology (2011) 36, 459-471; doi:10.1038/npp.2010.178; published online 6 October 2010