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.
摘要：
我们以前提供了证据支持存在一种新型的与瘦素无关的体重稳态仪（“引力仪”），该稳态仪可以感应体重，然后启动体重的稳态反馈调节。我们,在这里，假设这种反馈调节涉及CNS机制。为了确定由增加的负荷诱导的推定反馈信号的重要神经元群体，高脂饮食喂养的大鼠或小鼠腹膜内或皮下植入重量为体重的约15％（负荷）或约2.5％（对照）的胶囊。植入后3-5天，通过FosB的免疫组织化学检测评估脑/脑干不同部位的神经元激活。植入加重胶囊，皮下和腹膜内，在孤立道（mNTS）内侧核的特定神经元中诱导FosB，已知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），去甲肾上腺素神经元的典型模式。在功能研究中，我们特别消融了mNTS中的去甲肾上腺素神经元，这削弱了体重和食物摄入负荷增加的反馈调节。总之,增加的负荷似乎通过激活mNTS中的去甲肾上腺素神经元来减少体重和食物摄入。
