Increased hypothalamic serotonin turnover in inflammation-induced anorexia

J.T. Dwarkasing*, R.F. Witkamp, M.V. Boekschoten, M.C. ter Laak, M.S. Heins, K. van Norren

*Corresponding author for this work

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15 Citations (Scopus)

Abstract

Background: Anorexia can occur as a serious complication of disease. Increasing evidence suggests that inflammation plays a major role, along with a hypothalamic dysregulation characterized by locally elevated serotonin levels. The present study was undertaken to further explore the connections between peripheral inflammation, anorexia and hypothalamic serotonin metabolism and signaling pathways. First, we investigated the response of two hypothalamic neuronal cell lines to TNFα, IL-6 and LPS. Next, we studied transcriptomic changes and serotonergic activity in the hypothalamus of mice after intraperitoneal injection with TNFα, IL-6 or a combination of TNFα and IL-6. Results: In vitro, we showed that hypothalamic neurons responded to inflammatory mediators by releasing cytokines. This inflammatory response was associated with an increased serotonin release. Mice injected with TNFα and IL-6 showed decreased food intake, associated with altered expression of inflammation-related genes in the hypothalamus. In addition, hypothalamic serotonin turnover showed to be elevated in treated mice. Conclusions: Overall, our results underline that peripheral inflammation reaches the hypothalamus where it affects hypothalamic serotoninergic metabolism. These hypothalamic changes in serotonin pathways are associated with decreased food intake, providing evidence for a role of serotonin in inflammation-induced anorexia.

Original languageEnglish
Article number26
JournalBMC Neuroscience
Volume17
Issue number1
DOIs
Publication statusPublished - 2016

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  • Datasets

    TNFalpha and IL-6 induced anorexia: effects on serotonin turnover

    Dwarkasing, J. (Creator), Witkamp, R. (Creator), Boekschoten, M. (Creator), ter Laak, M. C. (Creator), Flik, G. (Creator) & van Norren, K. (Creator), Wageningen University, 31 May 2016

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