NF-κB signaling in tanycytes mediates inflammation-induced anorexia.,Molecular Metabolism

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NF-κB signaling in tanycytes mediates inflammation-induced anorexia.
Molecular Metabolism ( IF 7.0 ) Pub Date : 2020-05-21 , DOI: 10.1016/j.molmet.2020.101022
Mareike Böttcher ₁ , Helge Müller-Fielitz ₂ , Sivaraj M Sundaram ₁ , Sarah Gallet ₃ , Vanessa Neve ₁ , Kiseko Shionoya ₄ , Adriano Zager ₄ , Ning Quan ₅ , Xiaoyu Liu ₅ , Ruth Schmidt-Ullrich ₆ , Ronny Haenold ₇ , Jan Wenzel ₂ , Anders Blomqvist ₄ , David Engblom ₄ , Vincent Prevot ₃ , Markus Schwaninger ₂

Affiliation

Objectives

Infections, cancer, and systemic inflammation elicit anorexia. Despite the medical significance of this phenomenon, the question of how peripheral inflammatory mediators affect the central regulation of food intake is incompletely understood. Therefore, we have investigated the sickness behavior induced by the prototypical inflammatory mediator IL-1β.

Methods

IL-1β was injected intravenously. To interfere with IL-1β signaling, we deleted the essential modulator of NF-κB signaling (Nemo) in astrocytes and tanycytes.

Results

Systemic IL-1β increased the activity of the transcription factor NF-κB in tanycytes of the mediobasal hypothalamus (MBH). By activating NF-κB signaling, IL-1β induced the expression of cyclooxygenase-2 (Cox-2) and stimulated the release of the anorexigenic prostaglandin E₂ (PGE₂) from tanycytes. When we deleted Nemo in astrocytes and tanycytes, the IL-1β-induced anorexia was alleviated whereas the fever response and lethargy response were unchanged. Similar results were obtained after the selective deletion of Nemo exclusively in tanycytes.

Conclusions

Tanycytes form the brain barrier that mediates the anorexic effect of systemic inflammation in the hypothalamus.

中文翻译：

tanycytes 中的 NF-κB 信号传导介导炎症诱导的厌食症。

目标

感染、癌症和全身炎症会引起厌食。尽管这种现象具有医学意义，但外周炎症介质如何影响食物摄入的中枢调节的问题尚不完全清楚。因此，我们研究了典型炎症介质IL-1β诱导的疾病行为。

方法

静脉注射IL-1β。为了干扰 IL-1β 信号传导，我们删除了星形胶质细胞和单细胞中 NF-κB 信号传导的重要调节剂 ( Nemo )。

结果

全身性 IL-1β 增加了下丘脑内侧基底节 (MBH) 的单细胞中转录因子 NF-κB 的活性。通过激活 NF-κB 信号传导，IL-1β 诱导环氧合酶-2 (Cox-2) 的表达，并刺激单细胞释放抑制食欲的前列腺素 E ₂ (PGE ₂ )。当我们删除星形胶质细胞和单细胞中的Nemo时，IL-1β 诱导的厌食得到缓解，而发烧反应和嗜睡反应则没有变化。仅在单细胞中选择性删除Nemo后，获得了类似的结果。