Peripheral administration of prokineticin 2 potently reduces food intake and body weight in mice via the brainstem

Beale, KEL; Gardiner, JV; Bewick, GA; Hostomska, K.; Patel, NA; Hussain, SS; Jayasena, CN; Ebling, FJP; Jethwa, PH; Prosser, HM; Lattanzi, R.; Negri, L.; Ghatei, MA; Bloom, SR; Dhillo, WS

Abstract

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. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Citation

Beale, K., Gardiner, J., Bewick, G., Hostomska, K., Patel, N., Hussain, S., …Dhillo, W. (2013). Peripheral administration of prokineticin 2 potently reduces food intake and body weight in mice via the brainstem. British Journal of Pharmacology, 168(2), 403-410. https://doi.org/10.1111/j.1476-5381.2012.02191.x

• Journal Article Type: Article
• Acceptance Date: Aug 6, 2012
• Online Publication Date: Dec 20, 2012
• Publication Date: 2013-01
• Deposit Date: Jun 25, 2021
• Journal: British Journal of Pharmacology
• Print ISSN: 0007-1188
• Electronic ISSN: 1476-5381
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 168
• Issue: 2
• Pages: 403-410
• DOI: https://doi.org/10.1111/j.1476-5381.2012.02191.x
• Public URL: https://nottingham-repository.worktribe.com/output/3158358
• Publisher URL: https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/j.1476-5381.2012.02191.x