title: Increased hypothalamic serotonin turnover in inflammation-induced anorexia.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Nutrition and Pharmacology Group, Division of Human Nutrition, Wageningen University, Bomenweg 2, 6703HD, Wageningen, The Netherlands. jvalini@hotmail.com.
authors.forename: J T
authors.initials: JT
authors.lastname: Dwarkasing
authors.affiliation: Nutrition and Pharmacology Group, Division of Human Nutrition, Wageningen University, Bomenweg 2, 6703HD, Wageningen, The Netherlands.
authors.forename: R F
authors.initials: RF
authors.lastname: Witkamp
authors.affiliation: Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Bomenweg 2, 6703HD, Wageningen, The Netherlands.
authors.forename: M V
authors.initials: MV
authors.lastname: Boekschoten
authors.affiliation: Nutrition and Pharmacology Group, Division of Human Nutrition, Wageningen University, Bomenweg 2, 6703HD, Wageningen, The Netherlands.
authors.forename: M C
authors.initials: MC
authors.lastname: Ter Laak
authors.affiliation: Brains On-line, P.O. Box 4030, 9701 EA, Groningen, The Netherlands.
authors.forename: M S
authors.initials: MS
authors.lastname: Heins
authors.affiliation: Nutrition and Pharmacology Group, Division of Human Nutrition, Wageningen University, Bomenweg 2, 6703HD, Wageningen, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: van Norren
mesh_terms: D000818:Animals; D000855:Anorexia / Q000209:etiology* / Q000378:metabolism*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004435:Eating / Q000502:physiology; D020869:Gene Expression Profiling; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism*; D007249:Inflammation / Q000150:complications* / Q000378:metabolism*; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008297:Male; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D059467:Transcriptome; D014409:Tumor Necrosis Factor-alpha
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid