Saito R, So M, Motojima Y, Matsuura T, Yoshimura M, Hashimoto H, Yamamoto Y, Kusuhara K, Ueta Y
Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Department of Pediatrics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
J Neuroendocrinol. 2016 Sep;28(9). doi: 10.1111/jne.12400.
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.
外周食欲调节激素，如胰高血糖素样肽（GLP）-1、胆囊收缩素（CCK）-8和瘦素，可抑制食物摄入。新发现的食欲调节神经肽——核连蛋白-1，在外周组织和中枢神经系统中均有合成，尤其是在下丘脑和脑干的各个核团。在本研究中，我们通过Fos免疫组化法，检测了腹腔注射GLP-1和CCK-8以及以阈下剂量联合注射GLP-1和瘦素（通过测量食物摄入量确认）对大鼠下丘脑和脑干中核连蛋白-1免疫反应性（-IR）神经元的影响。腹腔注射GLP-1（100μg/kg）导致视上核（SON）、最后区（AP）和孤束核（NTS）中表达Fos免疫反应性的核连蛋白-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）中未增加。另一方面，腹腔注射CCK-8（50μg/kg）导致SON、PVN、AP和NTS中表达Fos免疫反应性的核连蛋白-1-IR神经元数量显著增加，但ARC或LHA中未增加。在生理盐水、GLP-1（33μg/kg）或瘦素处理的大鼠之间，未观察到下丘脑和脑干核团中表达Fos免疫反应性的核连蛋白-1-IR神经元百分比的差异。然而，联合注射GLP-1（33μg/kg）和瘦素导致AP和NTS中表达Fos免疫反应性的核连蛋白-1-IR神经元数量显著增加。此外，脑室注射反义核连蛋白-1预处理可显著减弱GLP-1、CCK-8和瘦素诱导的食物摄入量减少。这些结果表明，脑干中表达核连蛋白-1的神经元除了对CCK-8外，可能在感知外周GLP-1和瘦素水平方面也发挥重要作用，并且还可抑制大鼠的食物摄入。
