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NF-kappa B signaling in tanycytes mediates inflammation-induced anorexia

  • Boettcher, Mareike
  • Mueller-Fielitz, Helge
  • Sundaram, Sivaraj M.
  • Gallet, Sarah
  • Neve, Vanessa
  • Shionoya, Kiseko
  • Zager, Adriano
  • Quan, Ning
  • Liu, Xiaoyu
  • Schmidt-Ullrich, Ruth
  • Haenold, Ronny
  • Wenzel, Jan
  • Blomqvist, Anders
  • Engblom, David
  • Prevot, Vincent
  • Schwaninger, Markus
Publication Date
Jan 01, 2020
DOI: 10.1016/j.molmet.2020.101022
DiVA - Academic Archive On-line
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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-1 beta. Methods: IL-1 beta was injected intravenously. To interfere with IL-1 beta signaling, we deleted the essential modulator of NF-kappa B signaling (Nemo) in astrocytes and tanycytes. Results: Systemic IL-1 beta increased the activity of the transcription factor NF-kB in tanycytes of the mediobasal hypothalamus (MBH). By activating NF-kappa B signaling, IL-1 beta induced the expression of cyclooxygenase-2 (Cox-2) and stimulated the release of the anorexigenic prostaglandin E-2 (PGE(2)) from tanycytes. When we deleted Nemo in astrocytes and tanycytes, the IL-1 beta-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. (C) 2020 The Author(s). Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license ( / <p>Funding Agencies|Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [GRK1957, T-CRC 134, SPP1629, MU 3743/1-1]; Swedish Research CouncilSwedish Research Council [07879, 20725]; Swedish Brain Foundation; Swedish Cancer Foundation [2016/585]; Agence Nationale de la RechercheFrench National Research Agency (ANR) [ANR-15-CE14-0025-01, ANR-16-CE37-0006-02]; European Research Council (ERC) under the European Unions Horizon 2020 research and innovation programmeEuropean Research Council (ERC) [810331]; Velux Stiftung, Switzerland</p>

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