Activation of nesfatin-1-containing neurons in the hypothalamus and brainstem by peripheral administration of anorectic hormones and suppression of feeding via central nesfatin-1 in rats.
Activation of nesfatin-1-containing neurons in the hypothalamus and brainstem by peripheral administration of anorectic hormones and suppression of feeding via central nesfatin-1 in rats.
复制标题
通过外周给予大鼠食欲激素并通过中枢nesfatin-1抑制进食，激活下丘脑和脑干中含有nesfatin-1的神经元。
DOI：
10.1111/jne.12400
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发表时间：
2016
影响因子：
3.2
通讯作者：
Ueta Y.
中科院分区：
文献类型：
--
作者：
Saito R;So M;Motojima Y;Matsuura T;Yoshimura M;Hashimoto H;Yamamoto Y;Kusuhara K;Ueta Y.
外周厌食激素，如胰高血糖素样肽（GLP）-1，胆囊收缩素（CCK）-8和瘦素，抑制食物摄入。新发现的厌食神经肽nesfatin-1在外周组织和中枢神经系统中合成，特别是由下丘脑和脑干中的各种核团合成。在本研究中，我们通过Fos免疫组织化学检查了GLP-1和CCK-8腹腔给药以及GLP-1和瘦素以阈下剂量联合给药（通过摄食量测量证实）对大鼠下丘脑和脑干中nesfatin-1免疫反应（-IR）神经元的影响。GLP-1（100 μg/kg）腹腔给药导致视上核（SON）、最后区（AP）和孤束核（NTS）中表达Fos免疫反应性的nesfatin-1-IR神经元数量显著增加，但室旁核（PVN）、弓状核（ARC）或下丘脑外侧区（LHA）中未出现。另一方面，腹腔注射CCK-8（50 μg/kg）导致SON、PVN、AP和NTS中表达Fos免疫反应性的nesfatin-1-IR神经元数量显著增加，但ARC或LHA中未出现。在接受生理盐水、GLP-1（33 μg/kg）或瘦素处理的大鼠之间，未观察到下丘脑和脑干核中表达Fos免疫反应性的nesfatin-1-IR神经元百分比存在差异。然而，GLP-1（33 μg/kg）和瘦素联合给药导致AP和NTS中表达Fos免疫反应性的nesfatin-1-IR神经元数量显著增加。此外，通过i. c. v.给予反义nesfatin-1预处理，GLP-1、CCK-8和瘦素诱导的摄食量减少显著减弱。这些结果表明，脑干中表达nesfatin-1的神经元可能在感知外周GLP-1和瘦素以及CCK-8水平方面发挥重要作用，并抑制大鼠的摄食。
Peripheral anorectic hormones, such as glucagon‐like peptide (GLP)‐1, cholecystokinin (CCK)‐8 and leptin, suppress food intake. The newly‐identified anorectic neuropeptide, nesfatin‐1, is synthesised in both peripheral tissues and the central nervous system, particularly by various nuclei in the hypothalamus and brainstem. In the present study, we examined the effects of i.p. administration of GLP‐1 and CCK‐8 and co‐administrations of GLP‐1 and leptin at subthreshold doses as confirmed by measurement of food intake, on nesfatin‐1‐immunoreactive (‐IR) neurones in the hypothalamus and brainstem of rats by Fos immunohistochemistry. Intraperitoneal administration of GLP‐1 (100 μg/kg) caused significant increases in the number of nesfatin‐1‐IR neurones expressing Fos‐immunoreactivity in the supraoptic nucleus (SON), the area postrema (AP) and the nucleus tractus solitarii (NTS) but not in the paraventricular nucleus (PVN), the arcuate nucleus (ARC) or the lateral hypothalamic area (LHA). On the other hand, i.p. administration of CCK‐8 (50 μg/kg) resulted in marked increases in the number of nesfatin‐1‐IR neurones expressing Fos‐immunoreactivity in the SON, PVN, AP and NTS but not in the ARC or LHA. No differences in the percentage of nesfatin‐1‐IR neurones expressing Fos‐immunoreactivity in the nuclei of the hypothalamus and brainstem were observed between rats treated with saline, GLP‐1 (33 μg/kg) or leptin. However, co‐administration of GLP‐1 (33 μg/kg) and leptin resulted in significant increases in the number of nesfatin‐1‐IR neurones expressing Fos‐immunoreactivity in the AP and the NTS. Furthermore, decreased food intake induced by GLP‐1, CCK‐8 and leptin was attenuated significantly by pretreatment with i.c.v. administration of antisense nesfatin‐1. These results indicate that nesfatin‐1‐expressing neurones in the brainstem may play an important role in sensing peripheral levels of GLP‐1 and leptin in addition to CCK‐8, and also suppress food intake in rats.