title: Prokineticin 2 is a hypothalamic neuropeptide that potently inhibits food intake.
abstract: OBJECTIVE
  Prokineticin 2 (PK2) is a hypothalamic neuropeptide expressed in central nervous system areas known to be involved in food intake. We therefore hypothesized that PK2 plays a role in energy homeostasis.
  
  
  METHODS
  We investigated the effect of nutritional status on hypothalamic PK2 expression and effects of PK2 on the regulation of food intake by intracerebroventricular (ICV) injection of PK2 and anti-PK2 antibody. Subsequently, we investigated the potential mechanism of action by determining sites of neuronal activation after ICV injection of PK2, the hypothalamic site of action of PK2, and interaction between PK2 and other hypothalamic neuropeptides regulating energy homeostasis. To investigate PK2's potential as a therapeutic target, we investigated the effect of chronic administration in lean and obese mice.
  
  
  RESULTS
  Hypothalamic PK2 expression was reduced by fasting. ICV administration of PK2 to rats potently inhibited food intake, whereas anti-PK2 antibody increased food intake, suggesting that PK2 is an anorectic neuropeptide. ICV administration of PK2 increased c-fos expression in proopiomelanocortin neurons of the arcuate nucleus (ARC) of the hypothalamus. In keeping with this, PK2 administration into the ARC reduced food intake and PK2 increased the release of alpha-melanocyte-stimulating hormone (alpha-MSH) from ex vivo hypothalamic explants. In addition, ICV coadministration of the alpha-MSH antagonist agouti-related peptide blocked the anorexigenic effects of PK2. Chronic peripheral administration of PK2 reduced food and body weight in lean and obese mice.
  
  
  CONCLUSIONS
  This is the first report showing that PK2 has a role in appetite regulation and its anorectic effect is mediated partly via the melanocortin system.
authors.affiliation: Department of Investigative Medicine, Imperial College London, London, UK.
authors.forename: James V
authors.initials: JV
authors.lastname: Gardiner
authors.forename: Attia
authors.initials: A
authors.lastname: Bataveljic
authors.forename: Neekhil A
authors.initials: NA
authors.lastname: Patel
authors.forename: Gavin A
authors.initials: GA
authors.lastname: Bewick
authors.forename: Debabrata
authors.initials: D
authors.lastname: Roy
authors.forename: Daniel
authors.initials: D
authors.lastname: Campbell
authors.forename: Hannah C
authors.initials: HC
authors.lastname: Greenwood
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Murphy
authors.forename: Saira
authors.initials: S
authors.lastname: Hameed
authors.forename: Preeti H
authors.initials: PH
authors.lastname: Jethwa
authors.forename: Francis J P
authors.initials: FJ
authors.lastname: Ebling
authors.forename: Steven P
authors.initials: SP
authors.lastname: Vickers
authors.forename: Sharon
authors.initials: S
authors.lastname: Cheetham
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Ghatei
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Bloom
authors.forename: Waljit S
authors.initials: WS
authors.lastname: Dhillo
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D002149:Energy Intake / Q000187:drug effects*; D005768:Gastrointestinal Hormones / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology*; D005786:Gene Expression Regulation; D007031:Hypothalamus / Q000502:physiology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009479:Neuropeptides / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology*; D009765:Obesity / Q000503:physiopathology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
chemical_list: D005768:Gastrointestinal Hormones; D009479:Neuropeptides; C486586:Prok2 protein, mouse; D012333:RNA, Messenger; C513686:prokineticin 2, rat