Abstract
BackgroundAnorexia 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.ResultsIn 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.ConclusionsOverall, 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12868-016-0260-0) contains supplementary material, which is available to authorized users.
Highlights
IntroductionIncreasing evidence suggests that inflammation plays a major role, along with a hypothalamic dysregulation characterized by locally elevated serotonin levels
Anorexia can occur as a serious complication of disease
5-hydroxyindoleacetic acid (5-HIAA) were elevated after exposure to IL-6, TNFα and LPS in both cell lines. Both cell lines produced IL-6 when exposed to IL-6, since levels detected were four to sixfold higher than exposed levels
Summary
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. A chronically elevated increased inflammatory tone is considered one of the major drivers of anorexia in these diseases. Studies suggest that an ongoing elevated inflammatory tone in the hypothalamus, displaying the highest density of various cytokine receptors in the brain [1], is implicated in these disturbances in food intake. Cytokines and other pro-inflammatory signalling molecules from the periphery are able to reach the hypothalamus passing the blood brain barrier (BBB) [5,6,7].
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