Vanessa Neve, Anders Blomqvist, Markus Schwaninger, David Engblom, Jan Wenzel, Ruth Schmidt-Ullrich, Ronny Haenold, Sarah Gallet, Sivaraj Mohana Sundaram, Mareike Böttcher, Adriano Zager, Vincent Prevot, Kiseko Shionoya, Helge Müller-Fielitz, Xiaoyu Liu, Ning Quan, Prevot, Vincent, Lübeck University of Applied Sciences, German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Linköping University (LIU), Florida Atlantic University [Boca Raton], Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Leibniz Association, Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), and ANR-16-CE37-0006,HypNeurogen,Physiopathologie de la niche neurogénique hypothalamique(2016)
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., Graphical abstract Image 1, Highlights • Systemic IL-1β activates NF-κB in tanycytes. • IL-1β induces the expression of Ptgs2 (Cox-2) and the release of PGE2 from tanycytes. • NEMO-dependent NF-κB signaling in tanycytes is required for anorexia induced by IL-1β. • Tanycytes are not involved in fever and lethargy induced by IL-1β.