Neurosecretory Protein GL, a Hypothalamic Small Secretory Protein, Participates in Energy Homeostasis in Male Mice
Neurosecretory Protein GL, a Hypothalamic Small Secretory Protein, Participates in Energy Homeostasis in Male Mice
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DOI：
10.1210/en.2017-00064
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发表时间：
2017-05-01
期刊：
影响因子：
4.8
通讯作者：
Ukena, Kazuyoshi
中科院分区：
文献类型：
--
作者：
Matsuura, Daichi;Shikano, Kenshiro;Ukena, Kazuyoshi
我们最近从禽类下丘脑中鉴定出编码一种小分泌蛋白的互补 DNA，称为神经分泌蛋白 GL (NPGL)。对于小鸡来说，NPGL 会增加体重而不影响食物摄入量。数据库搜索表明 NPGL 在整个脊椎动物中都是保守的。然而，NPGL 在哺乳动物中的中心分布和功能作用仍有待阐明。在这项研究中，我们从小鼠下丘脑中鉴定出了编码 NPGL 的前体互补 DNA。定量逆转录聚合酶链反应和形态学分析表明，NPGL 前体信使 RNA 在下丘脑内侧基底层中强烈表达，NPGL 神经元特异性定位于下丘脑弓状核的后部。观察到 NPGL 免疫反应性纤维与弓状核吻端区的阿片黑皮素原神经元在解剖学上密切接触。 24 小时禁食后 NPGL 信使 RNA 表达升高，5 周高脂饮食喂养后 NPGL 信使 RNA 表达降低。此外，脑室内注射成熟的 NPGL 会增加食物摄入量，这表明其在喂养中发挥着重要作用。总而言之，这些发现报告了 NPGL 在哺乳动物大脑中的分布，并指出了这种神经肽在能量稳态中的重要作用。
We have recently identified from the avian hypothalamus a complementary DNA encoding a small secretory protein termed neurosecretory protein GL (NPGL). In chicks, NPGL increases body weight gain without affecting food intake. A database search reveals that NPGL is conserved throughout vertebrates. However, the central distribution and functional role of NPGL remains to be elucidated in mammals. In this study, we identified the precursor complementary DNA encoding NPGL from the mouse hypothalamus. Quantitative reverse transcription polymerase chain reaction and morphological analyses revealed that NPGL precursor messenger RNA is robustly expressed in the mediobasal hypothalamus with NPGL neurons specifically localized to the lateroposterior part of the arcuate nucleus in the hypothalamus. NPGL-immunoreactive fibers were observed in close anatomical contact with pro-opiomelanocortin neurons in the rostral region of the arcuate nucleus. NPGL messenger RNA expression was elevated by 24-hour fasting and reduced by feeding of a high-fat diet for 5 weeks. Furthermore, intracerebroventricular injection of mature NPGL increased food intake, pointing to an important role in feeding. Taken together, these findings report on the distribution of NPGL in the mammalian brain and point to an important role for this neuropeptide in energy homeostasis.