Prokineticin 2 is a hypothalamic neuropeptide that potently inhibits food intake

Gardiner, James V.; Bataveljic, Attia; Patel, Neekhil A.; Bewick, Gavin A.; Roy, Debabrata; Campbell, Daniel; Greenwood, Hannah C.; Murphy, Kevin G.; Hameed, Saira; Jethwa, Preeti H.; Ebling, Francis J.P.; Vickers, Steven P.; Cheetham, Sharon; Ghatei, Mohammad A.; Bloom, Stephen R.; Dhillo, Waljit S.

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. 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 intracerebro-ventricular (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. © 2010 by the American Diabetes Association.

Citation

Gardiner, J. V., Bataveljic, A., Patel, N. A., Bewick, G. A., Roy, D., Campbell, D., …Dhillo, W. S. (2010). Prokineticin 2 is a hypothalamic neuropeptide that potently inhibits food intake. Diabetes, 59(2), 397-406. https://doi.org/10.2337/db09-1198

• Journal Article Type: Article
• Acceptance Date: Nov 6, 2009
• Online Publication Date: Nov 23, 2009
• Publication Date: Jan 26, 2010
• Deposit Date: Jun 25, 2021
• Journal: Diabetes
• Print ISSN: 0012-1797
• Electronic ISSN: 1939-327X
• Publisher: American Diabetes Association
• Peer Reviewed: Peer Reviewed
• Volume: 59
• Issue: 2
• Pages: 397-406
• DOI: https://doi.org/10.2337/db09-1198
• Public URL: https://nottingham-repository.worktribe.com/output/3158394
• Publisher URL: https://diabetes.diabetesjournals.org/content/59/2/397