Investigation of the role of prokineticin 2, a newly identified potent inhibitor of food intake

Lead Research Organisation: Imperial College London
Department Name: Dept of Medicine

Abstract

Obesity is the major cause of early death in the UK, prematurely killing 1000 people per week. Despite great advances in knowledge, many of the factors which regulate appetite and body weight are unknown and to date there are no truly effective medical treatments for obesity. Evidence suggests that the recently identified novel chemical transmitter in the brain known as prokineticin-2 (PK-2) is important in appetite regulation. I will investigate the role of PK-2 in the control of appetite and the development of obesity. I will examine if PK-2 levels in the brain change in response to obesity and fasting. I will also determine the types of brain cells activated by PK-2 and also the effects of PK-2 in different regions of the brain. I will also investigate if increasing or decreasing the amount of PK-2 in the rat brain affects food intake. These studies are important as they will determine the mechanisms in the brain by which PK-2 affects food intake and may provide the basis for new drugs for the treatment of obesity.

Technical Summary

Prokineticin 2 (PK-2) is a newly identified hypothalamic neurotransmitter. PK-2 expression in the hypothalamus is highest in satiated and lowest in fasted animals. In pilot studies I have shown that PK-2 is the most potent inhibitor of food intake yet identified and that immunoblockade of PK-2 by intracerebroventricular administration of anti-PK-2 IgG increases feeding. Together, these data suggest that PK-2 has a physiological role in the regulation of food intake.

To determine the role and physiological importance of PK-2 in the control of appetite, I will:
1. Determine the responsiveness of PK-2 expression to specific alterations in energy balance.
2. Investigate the hypothalamic site of action of PK-2 and the neuronal pathways involved in PK-2 signalling.
3. Investigate the effects of PK-2 on long-term weight regulation in rats by over and under expression of hypothalamic PK-2 using adeno-associated virus mediated gene transfer.

Together, these experiments will help to determine the physiological importance of PK-2 in the hypothalamic regulation of food intake and may identify it as a useful target in the treatment of obesity.

Publications

10 25 50

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Hameed S (2009) Gut hormones and appetite control. in Oral diseases

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Hameed S (2010) Biology of kisspeptins. in Frontiers of hormone research

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Hameed S (2011) Kisspeptin and fertility. in The Journal of endocrinology

 
Description Programme Grant
Amount £45,000 (GBP)
Organisation AstraZeneca 
Sector Private
Country United Kingdom
Start  
 
Description This work received significant media attention as a press release 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact http://esciencenews.com/articles/2009/06/10/brain.molecule.reduces.food.intake http://www.news-medical.net/news/20090610/Discovery-of-new-appetite-suppressant-potential-anti-obesity-treatment.aspx http://www.endo-society.org/media/press/upload/PATEL_FINAL.pdf http://www.physorg.com/news163850449.html http://www.thaindian.com/newsportal/health/brain-molecule-that-helps-control-hunger-identified_100203480.html http://www.noscira.com/prensa.cfm?idIdioma=2&mS=239&mSS=242&idArticulo=549 http://medical.bizcommunity.com/Article/196/323/36852.html http://www.southasianews.com/NewsPrint.asp?nid=394074 http://www.naranjasoftware.com/article/Brain-Molecule-Reduces-Food-Intake.html http://news.oneindia.in/2009/06/11/brainmolecule-that-helps-control-hungeridentified.html http://www.foodproductdesign.com/news/2009/06/brain-molecule-reduces-hunger.aspx http://www.zeenews.com/news538418.html http://www.quantumhealth.com.au/index.php?option=com_content&task=view&id=91 http://89.234.40.242/news/newsarticle138.aspx

Significant peer group, media and lay interest in the findings.
Year(s) Of Engagement Activity 2009