Document Detail


Peripheral administration of prokineticin 2 potently reduces food intake and body weight in mice via the brainstem.
MedLine Citation:
PMID:  22935107     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: Prokineticin 2 (PK2) has recently been shown to acutely reduce food intake in rodents. We aimed to determine the CNS sites and receptors that mediate the anorectic effects of peripherally administered PK2 and its chronic effects on glucose and energy homeostasis.
EXPERIMENTAL APPROACH: We investigated neuronal activation following i.p. administration of PK2 using c-Fos-like immunoreactivity (CFL-IR). The anorectic effect of PK2 was examined in mice with targeted deletion of either prokineticin receptor 1 (PKR1) or prokineticin receptor 2 (PKR2), and in wild-type mice following administration of the PKR1 antagonist, PC1. The effect of IP PK2 administration on glucose homeostasis was investigated. Finally, the effect of long-term administration of PK2 on glucose and energy homeostasis in diet-induced obese (DIO) mice was determined.
KEY RESULTS: I.p. PK2 administration significantly increased CFL-IR in the dorsal motor vagal nucleus of the brainstem. The anorectic effect of PK2 was maintained in mice lacking the PKR2 but abolished in mice lacking PKR1 and in wild-type mice pre-treated with PC1. DIO mice treated chronically with PK2 had no changes in glucose levels but significantly reduced food intake and body weight compared to controls.
CONCLUSIONS AND IMPLICATIONS: Together, our data suggest that the anorectic effects of peripherally administered PK2 are mediated via the brainstem and this effect requires PKR1 but not PKR2 signalling. Chronic administration of PK2 reduces food intake and body weight in a mouse model of human obesity, suggesting that PKR1-selective agonists have potential to be novel therapeutics for the treatment of obesity.
Authors:
Kel Beale; J V Gardiner; G A Bewick; K Hostomska; N A Patel; S S Hussain; C N Jayasena; F J P Ebling; P H Jethwa; H M Prosser; R Lattanzi; L Negri; M A Ghatei; S R Bloom; W S Dhillo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  168     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-02     Completed Date:  2013-06-17     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  403-10     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Obesity Agents / administration & dosage*
Blood Glucose / analysis
Body Weight / drug effects
Brain Stem / drug effects*,  physiology
Eating / drug effects*
Female
Gastrointestinal Hormones / administration & dosage*
Male
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Neuropeptides / administration & dosage*
Obesity / drug therapy,  physiopathology
Proto-Oncogene Proteins c-fos / metabolism
Receptors, G-Protein-Coupled / physiology*
Grant Support
ID/Acronym/Agency:
CDF-2011-04-006//Department of Health; //Biotechnology and Biological Sciences Research Council; //Medical Research Council; //Wellcome Trust
Chemical
Reg. No./Substance:
0/Anti-Obesity Agents; 0/Blood Glucose; 0/Gastrointestinal Hormones; 0/Neuropeptides; 0/PKR1 protein, mouse; 0/PKR2 protein, mouse; 0/Prok2 protein, mouse; 0/Proto-Oncogene Proteins c-fos; 0/Receptors, G-Protein-Coupled
Comments/Corrections

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