NF-κB signaling in tanycytes mediates inflammation-induced anorexia

Mareike Böttcher; Helge Müller-Fielitz; Sivaraj M Sundaram; Sarah Gallet; Vanessa Neve; Kiseko Shionoya; Adriano Zager; Ning Quan; Xiaoyu Liu; Ruth Schmidt-Ullrich; Ronny Haenold; Jan Wenzel; Anders Blomqvist; David Engblom; Vincent Prevot; Markus Schwaninger

doi:10.1016/j.molmet.2020.101022

NF-κB signaling in tanycytes mediates inflammation-induced anorexia

Mareike Böttcher, Helge Müller-Fielitz, Sivaraj M Sundaram, Sarah Gallet, Vanessa Neve, Kiseko Shionoya, Adriano Zager, Ning Quan, Xiaoyu Liu, Ruth Schmidt-Ullrich, Ronny Haenold, Jan Wenzel, Anders Blomqvist, David Engblom, Vincent Prevot, Markus Schwaninger

Institut für Experimentelle und Klinische Pharmakologie und Toxikologie

38 Zitate (Scopus)

Abstract

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.

Originalsprache	Englisch
Aufsatznummer	101022
Zeitschrift	Molecular Metabolism
Jahrgang	39
Seiten (von - bis)	101022
ISSN	2212-8778
DOIs	https://doi.org/10.1016/j.molmet.2020.101022 https://doi.org/10.1016/j.molmet.2020.101022
Publikationsstatus	Veröffentlicht - 09.2020

Fördermittel

We would like to thank Ines Stölting and Frauke Spiecker for expert technical help, Kathrin Kalies for kind support with laser microdissection, Manolis Pasparakis, Cologne, for providing Nemo FL mice, Magdalena Götz, Munich, for providing GlastCreER T2 animals, and Martin Wessendorf, Minneapolis, for providing ppTRH antibody. This project has received funding from the Deutsche Forschungsgemeinschaft ( GRK1957 , T-CRC 134 to M.S.; SPP1629 , MU 3743/1-1 to H.M.F.); the Swedish Research Council (# 07879 and # 20725 ), the Swedish Brain Foundation , the Swedish Cancer Foundation (# 2016/585 ) to A.B.; the Agence Nationale de la Recherche ( ANR-15-CE14-0025-01 , ANR-16-CE37-0006-02 ) to V.P.; and the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No. 810331 ) to V. P. and M.S. R.H. received funding from the Velux Stiftung , Switzerland.

UN SDGs

Dieser Output leistet einen Beitrag zu folgendem(n) Ziel(en) für nachhaltige Entwicklung

SDG 3 – Gesundheit und Wohlergehen

Strategische Forschungsbereiche und Zentren

Forschungsschwerpunkt: Infektion und Entzündung - Zentrum für Infektions- und Entzündungsforschung Lübeck (ZIEL)

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Böttcher, M., Müller-Fielitz, H., Sundaram, S. M., Gallet, S., Neve, V., Shionoya, K., Zager, A., Quan, N., Liu, X., Schmidt-Ullrich, R., Haenold, R., Wenzel, J., Blomqvist, A., Engblom, D., Prevot, V., & Schwaninger, M. (2020). NF-κB signaling in tanycytes mediates inflammation-induced anorexia. Molecular Metabolism, 39, 101022. Artikel 101022. https://doi.org/10.1016/j.molmet.2020.101022, https://doi.org/10.1016/j.molmet.2020.101022

@article{9b31f42cb6cc4a52aeb51dbad5578f0b,

title = "NF-κB signaling in tanycytes mediates inflammation-induced anorexia",

abstract = "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.",

author = "Mareike B{\"o}ttcher and Helge M{\"u}ller-Fielitz and Sundaram, \{Sivaraj M\} and Sarah Gallet and Vanessa Neve and Kiseko Shionoya and Adriano Zager and Ning Quan and Xiaoyu Liu and Ruth Schmidt-Ullrich and Ronny Haenold and Jan Wenzel and Anders Blomqvist and David Engblom and Vincent Prevot and Markus Schwaninger",

year = "2020",

month = sep,

doi = "10.1016/j.molmet.2020.101022",

language = "English",

volume = "39",

pages = "101022",

journal = "Molecular Metabolism",

issn = "2212-8778",

}

Böttcher, M, Müller-Fielitz, H, Sundaram, SM, Gallet, S, Neve, V, Shionoya, K, Zager, A, Quan, N, Liu, X, Schmidt-Ullrich, R, Haenold, R, Wenzel, J, Blomqvist, A, Engblom, D, Prevot, V & Schwaninger, M 2020, 'NF-κB signaling in tanycytes mediates inflammation-induced anorexia', Molecular Metabolism, Jg. 39, 101022, S. 101022. https://doi.org/10.1016/j.molmet.2020.101022, https://doi.org/10.1016/j.molmet.2020.101022

TY - JOUR

T1 - NF-κB signaling in tanycytes mediates inflammation-induced anorexia

AU - Böttcher, Mareike

AU - Müller-Fielitz, Helge

AU - Sundaram, Sivaraj M

AU - Gallet, Sarah

AU - Neve, Vanessa

AU - Shionoya, Kiseko

AU - Zager, Adriano

AU - Quan, Ning

AU - Liu, Xiaoyu

AU - Schmidt-Ullrich, Ruth

AU - Haenold, Ronny

AU - Wenzel, Jan

AU - Blomqvist, Anders

AU - Engblom, David

AU - Prevot, Vincent

AU - Schwaninger, Markus

PY - 2020/9

Y1 - 2020/9

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85086133000

UR - https://www.mendeley.com/catalogue/f2cdb34f-a93f-3ef8-bfda-88011cf23679/

U2 - 10.1016/j.molmet.2020.101022

DO - 10.1016/j.molmet.2020.101022

M3 - Journal articles

C2 - 32446877

AN - SCOPUS:85086133000

SN - 2212-8778

VL - 39

SP - 101022

JO - Molecular Metabolism

JF - Molecular Metabolism

M1 - 101022

ER -

NF-κB signaling in tanycytes mediates inflammation-induced anorexia

Abstract

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