Imperial College London

DrGavinBewick

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Honorary Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 3313 3086g.bewick

 
 
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Location

 

6N5Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Gardiner:2009:10.2337/db09-1198,
author = {Gardiner, JV and Bataveljic, A and Patel, NA and Bewick, GA and Roy, D and Campbell, D and Greenwood, HC and Murphy, KG and Hameed, S and Jethwa, PH and Ebling, FJP and Vickers, SP and Cheetham, S and Ghatei, MA and Bloom, SR and Dhillo, WS},
doi = {10.2337/db09-1198},
journal = {Diabetes},
pages = {397--406},
title = {Prokineticin 2 Is a Hypothalamic Neuropeptide That Potently Inhibits Food Intake},
url = {http://dx.doi.org/10.2337/db09-1198},
volume = {59},
year = {2009}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - 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.RESEARCH DESIGN AND 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 α-melanocyte–stimulating hormone (α-MSH) from ex vivo hypothalamic explants. In addition, ICV coadministration of the α-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.
AU - Gardiner,JV
AU - Bataveljic,A
AU - Patel,NA
AU - Bewick,GA
AU - Roy,D
AU - Campbell,D
AU - Greenwood,HC
AU - Murphy,KG
AU - Hameed,S
AU - Jethwa,PH
AU - Ebling,FJP
AU - Vickers,SP
AU - Cheetham,S
AU - Ghatei,MA
AU - Bloom,SR
AU - Dhillo,WS
DO - 10.2337/db09-1198
EP - 406
PY - 2009///
SN - 0012-1797
SP - 397
TI - Prokineticin 2 Is a Hypothalamic Neuropeptide That Potently Inhibits Food Intake
T2 - Diabetes
UR - http://dx.doi.org/10.2337/db09-1198
UR - http://hdl.handle.net/10044/1/30486
VL - 59
ER -