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

L. Maletínská, V. Nagelová, A. Tichá, J. Zemenová, Z. Pirník, M. Holubová, A. Špolcová, B. Mikulášková, M. Blechová, D. Sýkora, Z. Lacinová, M. Haluzík, B. Železná, J. Kuneš,

. 2015 ; 39 (6) : 986-93. [pub] 20150316

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc16020938
E-zdroje Online Plný text

NLK Free Medical Journals od 2005 do Před 5 lety
ProQuest Central od 2005-01-01 do Před 1 rokem
Open Access Digital Library od 1997-01-01
Medline Complete (EBSCOhost) od 2005-01-01 do 2015-11-30
Health & Medicine (ProQuest) od 2005-01-01 do Před 1 rokem
Psychology Database (ProQuest) od 2005-01-01 do Před 1 rokem
Public Health Database (ProQuest) od 2000-01-01 do Před 1 rokem

Odkazy

PubMed 25771926
DOI 10.1038/ijo.2015.28
Knihovny.cz E-zdroje

OBJECTIVES: 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. RESULTS: 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. CONCLUSIONS: 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.

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