人下丘脑的核结合蛋白 2/nesfatin-1 在肥胖患者中减少，并与催产素、血管加压素、黑色素浓缩激素、可卡因和安非他命调节转录本共定位。

Nucleobindin-2/Nesfatin-1 in the Human Hypothalamus Is Reduced in Obese Subjects and Colocalizes with Oxytocin, Vasopressin, Melanin-Concentrating Hormone, and Cocaine- and Amphetamine-Regulated Transcript.

机构信息

Department of Anatomy-Histology-Embryology, School of Medicine, University of Patras, Patras, Greece,

Department of Anatomy-Histology-Embryology, School of Medicine, University of Patras, Patras, Greece.

出版信息

Neuroendocrinology. 2019;108(3):190-200. doi: 10.1159/000496731. Epub 2019 Jan 9.

DOI:10.1159/000496731

PMID:30625474

Abstract

BACKGROUND/AIMS: Nesfatin-1, processed from nucleobindin-2 (NUCB2), is a potent anorexigenic peptide being expressed in rodent hypothalamic nuclei and involved in the regulation of feeding behavior and body weight in animals. The present study aimed to investigate NUCB2/nesfatin-1 protein expression in the human hypothalamus as well as its correlation with body weight.

METHODS

Sections of hypothalamus and adjacent cholinergic basal forebrain nuclei, including the nucleus basalis of Meynert (NBM) and the diagonal band of Broca (DBB), from 25 autopsy cases (17 males, 8 females; 8 lean, 9 overweight, 8 obese) were examined using immunohistochemistry and double immunofluorescence labeling.

RESULTS

Prominent NUCB2/nesfatin-1 immunoexpression was detected in supraoptic, paraventricular, and infundibular nuclei, lateral hypothalamic area (LHA)/perifornical region, and NBM/DBB. NUCB2/nesfatin-1 was found to extensively colocalize with (a) oxytocin and vasopressin in paraventricular and supraoptic nuclei, (b) melanin-concentrating hormone in the LHA, and (c) cocaine- and amphetamine-regulated transcript in infundibular and paraventricular nuclei and LHA. Interestingly, in the LHA, NUCB2/nesfatin-1 protein expression was significantly decreased in obese, compared with lean (p < 0.01) and overweight (p < 0.05) subjects.

CONCLUSIONS

The findings of the present study are suggestive of a potential role for NUCB2/nesfatin-1 as an integral regulator of food intake and energy homeostasis in the human hypothalamus. In the LHA, an appetite- and reward-related brain area, reduced NUCB2/nesfatin-1 immunoexpression may contribute to dysregulation of homeostatic and/or hedonic feeding behavior and obesity. NUCB2/nesfatin-1 localization in NBM/DBB might imply its participation in the neuronal circuitry controlling cognitive influences on food intake and give impetus towards unraveling additional biological actions of NUCB2/nesfatin-1 in human neuronal networks.

摘要

背景/目的：Nesfatin-1 是由核结合蛋白 2（NUCB2）加工而成的一种有效的厌食肽，在啮齿动物下丘脑核中表达，并参与动物摄食行为和体重的调节。本研究旨在研究人类下丘脑中 NUCB2/nesfatin-1 蛋白的表达及其与体重的关系。

方法

对 25 例尸检标本（男性 17 例，女性 8 例；瘦 8 例，超重 9 例，肥胖 8 例）的下丘脑及相邻胆碱能基底前脑核，包括基底核（NBM）和 Broca 斜带（DBB）进行免疫组织化学和双重免疫荧光标记。

结果

在室旁核、视上核和漏斗核、外侧下丘脑区（LHA）/穹隆周区和 NBM/DBB 中检测到明显的 NUCB2/nesfatin-1 免疫反应。NUCB2/nesfatin-1 与（a）室旁核和视上核中的催产素和加压素，（b）LHA 中的黑色素浓缩激素，（c）漏斗核和室旁核及 LHA 中的可卡因和安非他命调节转录物广泛共定位。有趣的是，在 LHA 中，与瘦（p < 0.01）和超重（p < 0.05）受试者相比，肥胖受试者的 NUCB2/nesfatin-1 蛋白表达显著降低。

结论

本研究结果提示 NUCB2/nesfatin-1 在下丘脑作为调节食物摄入和能量平衡的整体调节剂的潜在作用。在 LHA 中，一种与食欲和奖励相关的大脑区域，NUCB2/nesfatin-1 免疫反应的减少可能导致稳态和/或享乐性摄食行为的失调和肥胖。NUCB2/nesfatin-1 在 NBM/DBB 的定位可能暗示其参与控制认知对食物摄入影响的神经元回路，并促使人们进一步揭示 NUCB2/nesfatin-1 在人类神经元网络中的其他生物学作用。