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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

Language English Country England, Great Britain

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc16020938
E-resources Online Full text

NLK Free Medical Journals from 2005 to 5 years ago
ProQuest Central from 2005-01-01 to 1 year ago
Open Access Digital Library from 1997-01-01
Medline Complete (EBSCOhost) from 2005-01-01 to 2015-11-30
Health & Medicine (ProQuest) from 2005-01-01 to 1 year ago
Psychology Database (ProQuest) from 2005-01-01 to 1 year ago
Public Health Database (ProQuest) from 2000-01-01 to 1 year ago

Links

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

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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$a OBJECTIVES: Obesity is a frequent metabolic disorder but an effective therapy is still scarce. Anorexigenic neuropeptides produced and acting in the brain have the potential to decrease food intake and ameliorate obesity but are ineffective after peripheral application. We have designed lipidized analogs of prolactin-releasing peptide (PrRP), which is involved in energy balance regulation as demonstrated by obesity phenotypes of both PrRP- and PrRP-receptor-knockout mice. RESULTS: Lipidized PrRP analogs showed binding affinity and signaling in PrRP receptor-expressing cells similar to natural PrRP. Moreover, these analogs showed high binding affinity also to anorexigenic neuropeptide FF-2 receptor. Peripheral administration of myristoylated and palmitoylated PrRP analogs to fasted mice induced strong and long-lasting anorexigenic effects and neuronal activation in the brain areas involved in food intake regulation. Two-week-long subcutaneous administration of palmitoylated PrRP31 and myristoylated PrRP20 lowered food intake, body weight and improved metabolic parameters, and attenuated lipogenesis in mice with diet-induced obesity. CONCLUSIONS: Our data suggest that the lipidization of PrRP enhances stability and mediates its effect in central nervous system. Strong anorexigenic and body-weight-reducing effects make lipidized PrRP an attractive candidate for anti-obesity treatment.
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$a Pirník, Z $u 1] Antiobesity Peptides, Institute of Organic Chemistry and Biochemistry, AS CR, Prague, Czech Republic [2] Laboratory of Functional Neuromorphology, Institute of Experimental Endocrinology, SAS, Bratislava, Slovak Republic [3] Department of Human and Clinical Pharmacology, University of Veterinary Medicine, Košice, Slovak Republic.
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