Novel lipidized analogs of prolactin-releasing peptide have prolonged half-lives and exert anti-obesity effects after peripheral administration

International Journal of Obesity : Journal of the International Association for the Study of Obesity
L MaletínskáJ Kuneš

Abstract

Obesity is a frequent metabolic disorder but an effective therapy is still scarce. Anorexigenic neuropeptides produced and acting in the brain have the potential to decrease food intake and ameliorate obesity but are ineffective after peripheral application. We have designed lipidized analogs of prolactin-releasing peptide (PrRP), which is involved in energy balance regulation as demonstrated by obesity phenotypes of both PrRP- and PrRP-receptor-knockout mice. Lipidized PrRP analogs showed binding affinity and signaling in PrRP receptor-expressing cells similar to natural PrRP. Moreover, these analogs showed high binding affinity also to anorexigenic neuropeptide FF-2 receptor. Peripheral administration of myristoylated and palmitoylated PrRP analogs to fasted mice induced strong and long-lasting anorexigenic effects and neuronal activation in the brain areas involved in food intake regulation. Two-week-long subcutaneous administration of palmitoylated PrRP31 and myristoylated PrRP20 lowered food intake, body weight and improved metabolic parameters, and attenuated lipogenesis in mice with diet-induced obesity. Our data suggest that the lipidization of PrRP enhances stability and mediates its effect in central nervous system. S...Continue Reading

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Citations

Feb 26, 2016·The Journal of Endocrinology·Martina HolubováLenka Maletínská
Jul 16, 2016·The Journal of Endocrinology·Jaroslav KunešLenka Maletínská
Jul 28, 2016·Molecular and Cellular Endocrinology·B MikuláškováJ Kuneš
Sep 14, 2016·Annual Review of Pharmacology and Toxicology·Carles Corbi-VergePhilip M Kim
Dec 15, 2016·Bioanalysis·Jana ZemenováJaroslav Kuneš
Dec 14, 2017·Journal of Molecular Endocrinology·Martina HolubováBlanka Železná
Jan 18, 2019·Biological Chemistry·Sven HofmannAnnette G Beck-Sickinger
Nov 27, 2018·The Journal of Endocrinology·Lenka MaletínskáJaroslav Kuneš
Oct 28, 2019·International Journal of Molecular Sciences·Veronika PražienkováLenka Maletínská
Jan 29, 2019·Journal of Alzheimer's Disease : JAD·Veronika PražienkováLenka Maletínská
Sep 5, 2020·International Journal of Molecular Sciences·Anna ZmeškalováLenka Maletínská
Dec 17, 2020·Frontiers in Endocrinology·L KořínkováLenka Maletínská
Aug 16, 2019·ACS Medicinal Chemistry Letters·Elsa PflimlinWeijun Shen

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