Biochemistry and Molecular Biology

Lenka Maletínská

Anorexigenic neuropeptides are potential anti-obesitics but they are unable to exert their exclusively central effect after peripheral administration. In our recent studies, we demonstrated that lipidized prolactin-releasing peptide (PrRP) analogs bound to PrRP receptor GPR10 and neuropeptide FF receptor NPFF2, decreased body weight and ameliorated metabolic parameters in rodent models of obesity after peripheral administration. Our preliminary results suggested possible involvement of receptors of other anorexigenic peptides. In this project, we aim to test new series of lipidized PrRP analogs and compare their affinity to and signaling in cells with GPR10, NPFF2 and off-target receptors. Their effect on food intake will be explored in knock-out (KO) GPR10 and NPFF2 mice and in intact animals without/after blockade of potent off-target receptors. Finally, effect of repeated administration of the most potent lipidized PrRP analogs to KO and control mice to elucidate their mechanism of action.