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BMC Neurosci. 2016 May 20;17(1):26. doi: 10.1186/s12868-016-0260-0.

Increased hypothalamic serotonin turnover in inflammation-induced anorexia.

Author information

1
Nutrition and Pharmacology Group, Division of Human Nutrition, Wageningen University, Bomenweg 2, 6703HD, Wageningen, The Netherlands. jvalini@hotmail.com.
2
Nutrition and Pharmacology Group, Division of Human Nutrition, Wageningen University, Bomenweg 2, 6703HD, Wageningen, The Netherlands.
3
Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Bomenweg 2, 6703HD, Wageningen, The Netherlands.
4
Brains On-line, P.O. Box 4030, 9701 EA, Groningen, The Netherlands.

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.

PMID:
27207102
PMCID:
PMC4875640
DOI:
10.1186/s12868-016-0260-0
[Indexed for MEDLINE]
Free PMC Article

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