Reduction of body weight by increased loading is associated with activation of norepinephrine neurones in the medial nucleus of the solitary tract

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC
Jovana Zlatkovic, Adrià Dalmau Gasull, Daniel Hägg, Ferran Font-Gironès, Jakob Bellman, Björn Meister, Vilborg Palsdottir, Johan Ruud, Claes Ohlsson, Suzanne L. Dickson, Fredrik Anesten, John-Olov Jansson
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Abstract

We previously provided evidence supporting the existence of a novel leptin-independent body weight homeostat (“the gravitostat”) that senses body weight and then initiates a homeostatic feed-back regulation of body weight. We, herein, hypothesize that this feed-back regulation involves a CNS mechanism. To identify populations of neurones of importance for the putative feed-back signal induced by increased loading, high-fat diet-fed rats or mice were implanted intraperitoneally or subcutaneously with capsules weighing ∼15% (Load) or ∼2.5% (Control) of body weight. At 3–5 days after implantation, neuronal activation was assessed in different parts of the brain/brainstem by immunohistochemical detection of FosB. Implantation of weighted capsules, both subcutaneous and intraperitoneal, induced FosB in specific neurones in the medial nucleus of the solitary tract (mNTS), known to integrate information about the metabolic status of the body. These neurones also expressed tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DbH), a pattern typical of norepinephrine neurones. In functional studies, we specifically ablated norepinephrine neurones in mNTS, which attenuated the feed-back regulation of increased load on body weight and food intake. In conclusion, increased load appears to reduce body weight and food intake via activation of norepinephrine neurones in the mNTS.

Abstract Image

通过增加负荷来减轻体重与孤束内侧核中去甲肾上腺素神经元的激活有关。
我们之前提供的证据支持一种新的瘦素非依赖性体重稳态器(“妊娠稳态器”)的存在,它可以感知体重,然后启动体重的稳态反馈调节。在此,我们假设这种反馈调节涉及中枢神经系统机制。为了确定对负荷增加诱导的假定反馈信号具有重要意义的神经元群体,高脂肪饮食喂养的大鼠或小鼠被腹膜内或皮下植入重量为体重~15%(负荷)或~2.5%(对照)的胶囊。3-5 植入后几天,通过FosB的免疫组织化学检测来评估大脑/脑干不同部位的神经元激活。皮下和腹膜内植入加重胶囊,在孤束内侧核(mNTS)的特定神经元中诱导FosB,已知该神经元整合有关身体代谢状态的信息。这些神经元还表达酪氨酸羟化酶(TH)和多巴胺β羟化酶(DbH),这是去甲肾上腺素神经元的典型模式。在功能研究中,我们专门切除了mNTS中的去甲肾上腺素神经元,这减弱了对体重和食物摄入负荷增加的反馈调节。总之,负荷增加似乎通过激活mNTS中的去甲肾上腺素神经元来减少体重和食物摄入。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.20
自引率
4.30%
发文量
567
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