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Novel lipidized analogs of prolactin-releasing peptide have prolonged half-lives and exert anti-obesity effects after peripheral administration
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SYSNO ASEP 0449769 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Novel lipidized analogs of prolactin-releasing peptide have prolonged half-lives and exert anti-obesity effects after peripheral administration Author(s) Maletínská, L. (CZ)
Nagelová, V. (CZ)
Tichá, A. (CZ)
Zemenová, J. (CZ)
Pirník, Z. (SK)
Holubová, M. (CZ)
Špolcová, A. (CZ)
Mikulášková, Barbora (FGU-C)
Blechová, M. (CZ)
Sýkora, D. (CZ)
Lacinová, Z. (CZ)
Haluzík, M. (CZ)
Železná, B. (CZ)
Kuneš, Jaroslav (FGU-C) RID, ORCIDSource Title International Journal of Obesity. - : Springer - ISSN 0307-0565
Roč. 39, č. 6 (2015), s. 986-993Number of pages 8 s. Language eng - English Country GB - United Kingdom Keywords food intake ; prolactin-releasing peptide ; GPR10 receptor Subject RIV CE - Biochemistry R&D Projects TE01020028 GA TA ČR - Technology Agency of the Czech Republic (TA ČR) Institutional support FGU-C - RVO:67985823 UT WOS 000356039500016 EID SCOPUS 84930762263 DOI 10.1038/ijo.2015.28 Annotation 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. Strong anorexigenic and body-weight-reducing effects make lipidized PrRP an attractive candidate for anti-obesity treatment Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2016
Number of the records: 1