title: Novel lipidized analogs of prolactin-releasing peptide have prolonged half-lives and exert anti-obesity effects after peripheral administration.
abstract: OBJECTIVE
  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.
authors.affiliation: Antiobesity Peptides, Institute of Organic Chemistry and Biochemistry, AS CR, Prague, Czech Republic.
authors.forename: L
authors.initials: L
authors.lastname: Maletínská
authors.affiliation: Antiobesity Peptides, Institute of Organic Chemistry and Biochemistry, AS CR, Prague, Czech Republic.
authors.forename: V
authors.initials: V
authors.lastname: Nagelová
authors.affiliation: Antiobesity Peptides, Institute of Organic Chemistry and Biochemistry, AS CR, Prague, Czech Republic.
authors.forename: A
authors.initials: A
authors.lastname: Tichá
authors.affiliation: 1] Antiobesity Peptides, Institute of Organic Chemistry and Biochemistry, AS CR, Prague, Czech Republic [2] Department of Analytical Chemistry, University of Chemistry and Technology, Prague, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Zemenová
authors.affiliation: 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.
authors.forename: Z
authors.initials: Z
authors.lastname: Pirník
authors.affiliation: Antiobesity Peptides, Institute of Organic Chemistry and Biochemistry, AS CR, Prague, Czech Republic.
authors.forename: M
authors.initials: M
authors.lastname: Holubová
authors.affiliation: Antiobesity Peptides, Institute of Organic Chemistry and Biochemistry, AS CR, Prague, Czech Republic.
authors.forename: A
authors.initials: A
authors.lastname: Špolcová
authors.affiliation: 1] Antiobesity Peptides, Institute of Organic Chemistry and Biochemistry, AS CR, Prague, Czech Republic [2] Institute of Physiology, AS CR, Prague, Czech Republic.
authors.forename: B
authors.initials: B
authors.lastname: Mikulášková
authors.affiliation: Antiobesity Peptides, Institute of Organic Chemistry and Biochemistry, AS CR, Prague, Czech Republic.
authors.forename: M
authors.initials: M
authors.lastname: Blechová
authors.affiliation: Department of Analytical Chemistry, University of Chemistry and Technology, Prague, Czech Republic.
authors.forename: D
authors.initials: D
authors.lastname: Sýkora
authors.affiliation: Third Department of Medicine, Charles University in Prague, Prague, Czech Republic.
authors.forename: Z
authors.initials: Z
authors.lastname: Lacinová
authors.affiliation: Third Department of Medicine, Charles University in Prague, Prague, Czech Republic.
authors.forename: M
authors.initials: M
authors.lastname: Haluzík
authors.affiliation: Antiobesity Peptides, Institute of Organic Chemistry and Biochemistry, AS CR, Prague, Czech Republic.
authors.forename: B
authors.initials: B
authors.lastname: Železná
authors.affiliation: 1] Antiobesity Peptides, Institute of Organic Chemistry and Biochemistry, AS CR, Prague, Czech Republic [2] Institute of Physiology, AS CR, Prague, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Kuneš
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D001069:Appetite Regulation; D004435:Eating; D004734:Energy Metabolism; D006207:Half-Life; D008055:Lipids / Q000737:chemistry*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000517:prevention & control*; D056690:Prolactin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: D019440:Anti-Obesity Agents; D008055:Lipids; D056690:Prolactin-Releasing Hormone