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Lipidized analogs of prolactin-releasing peptide as potential agents for obesity therapy: search for mechanism of action
Karnošová, Alena ; Maletínská, Lenka (advisor) ; Žáková, Lenka (referee) ; Janovská, Petra (referee)
Obesity is a common metabolic condition that is becoming more prevalent globally, but current treatments have limitations. Prolactin-releasing peptide (PrRP), a neuropeptide that reduces food intake after administration to the third ventricle, loses this ability when administered peripherally. However, lipidization of peptides enhances their stability in the bloodstream and facilitates their central effect after peripheral administration. We developed lipidized analogs of PrRP, which have high potential as a treatment option for obesity. We previously demonstrated that peripheral administration of lipidized PrRP analogs led to a substantial reduction in food intake and body weight in mice, with palm-PrRP31 and palm11 -PrRP31 emerging as key analogs. In this study, we aimed to further investigate the mechanisms underlying the effects of these two PrRP31 analogs in vitro. Natural PrRP31 binds to its receptor GPR10 and with high affinity to neuropeptide FF receptor type 2 (NPFFR2), which are both expressed in regions involved in food intake regulation. The palmitoylation of PrRP31 increased their binding and agonist properties for both GPR10 and NPFFR2 receptors. Lipidized analogs exhibited a stronger affinity also for another neuropeptide FF receptor, NPFFR1, suggesting that NPFFR1 could be a new potential...
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