title: Visfatin induces sickness responses in the brain.
abstract: OBJECTIVE
  Visfatin, also known as nicotiamide phosphoribosyltransferase or pre-B cell colony enhancing factor, is a pro-inflammatory cytokine whose serum level is increased in sepsis and cancer as well as in obesity. Here we report a pro-inflammatory role of visfatin in the brain, to mediate sickness responses including anorexia, hyperthermia and hypoactivity.
  
  
  METHODS
  Rats were intracerebroventricularly (ICV) injected with visfatin, and changes in food intake, body weight, body temperature and locomotor activity were monitored. Real-time PCR was applied to determine the expressions of pro-inflammatory cytokines, proopiomelanocortin (POMC) and prostaglandin-synthesizing enzymes in their brain. To determine the roles of cyclooxygenase (COX) and melanocortin in the visfatin action, rats were ICV-injected with visfatin with or without SHU9119, a melanocortin receptor antagonist, or indomethacin, a COX inhibitor, and their sickness behaviors were evaluated.
  
  
  RESULTS
  Administration of visfatin decreased food intake, body weight and locomotor activity and increased body temperature. Visfatin evoked significant increases in the levels of pro-inflammatory cytokines, prostaglandin-synthesizing enzymes and POMC, an anorexigenic neuropeptide. Indomethacin attenuated the effects of visfatin on hyperthermia and hypoactivity, but not anorexia. Further, SHU9119 blocked visfatin-induced anorexia but did not affect hyperthermia or hypoactivity.
  
  
  CONCLUSIONS
  Visfatin induced sickness responses via regulation of COX and the melanocortin pathway in the brain.
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan, Republic of Korea.
authors.forename: Byong Seo
authors.initials: BS
authors.lastname: Park
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Jin
authors.forename: Joong Jean
authors.initials: JJ
authors.lastname: Park
authors.forename: Jeong Woo
authors.initials: JW
authors.lastname: Park
authors.forename: Il Seong
authors.initials: IS
authors.lastname: Namgoong
authors.forename: Young Il
authors.initials: YI
authors.lastname: Kim
authors.forename: Byung Ju
authors.initials: BJ
authors.lastname: Lee
authors.forename: Jae Geun
authors.initials: JG
authors.lastname: Kim
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D016207:Cytokines; D004435:Eating / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced*; D053486:Melanocortins / Q000378:metabolism; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D054409:Nicotinamide Phosphoribosyltransferase / Q000008:administration & dosage / Q000009:adverse effects*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D053486:Melanocortins; C103272:SHU 9119; D009074:Melanocyte-Stimulating Hormones; D011451:Prostaglandin-Endoperoxide Synthases; D054409:Nicotinamide Phosphoribosyltransferase; D007213:Indomethacin