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Novel lipidized analogs of prolactin-releasing peptide have prolonged half-lives and exert anti-obesity effects after peripheral administration.
Maletínská, L; Nagelová, V; Tichá, A; Zemenová, J; Pirník, Z; Holubová, M; Spolcová, A; Mikulásková, B; Blechová, M; Sýkora, D; Lacinová, Z; Haluzík, M; Zelezná, B; Kunes, J.
Afiliación
  • Maletínská L; Antiobesity Peptides, Institute of Organic Chemistry and Biochemistry, AS CR, Prague, Czech Republic.
  • Nagelová V; Antiobesity Peptides, Institute of Organic Chemistry and Biochemistry, AS CR, Prague, Czech Republic.
  • Tichá A; Antiobesity Peptides, Institute of Organic Chemistry and Biochemistry, AS CR, Prague, Czech Republic.
  • Zemenová J; 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.
  • Pirník Z; 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
  • Holubová M; Antiobesity Peptides, Institute of Organic Chemistry and Biochemistry, AS CR, Prague, Czech Republic.
  • Spolcová A; Antiobesity Peptides, Institute of Organic Chemistry and Biochemistry, AS CR, Prague, Czech Republic.
  • Mikulásková B; 1] Antiobesity Peptides, Institute of Organic Chemistry and Biochemistry, AS CR, Prague, Czech Republic [2] Institute of Physiology, AS CR, Prague, Czech Republic.
  • Blechová M; Antiobesity Peptides, Institute of Organic Chemistry and Biochemistry, AS CR, Prague, Czech Republic.
  • Sýkora D; Department of Analytical Chemistry, University of Chemistry and Technology, Prague, Czech Republic.
  • Lacinová Z; Third Department of Medicine, Charles University in Prague, Prague, Czech Republic.
  • Haluzík M; Third Department of Medicine, Charles University in Prague, Prague, Czech Republic.
  • Zelezná B; Antiobesity Peptides, Institute of Organic Chemistry and Biochemistry, AS CR, Prague, Czech Republic.
  • Kunes J; 1] Antiobesity Peptides, Institute of Organic Chemistry and Biochemistry, AS CR, Prague, Czech Republic [2] Institute of Physiology, AS CR, Prague, Czech Republic.
Int J Obes (Lond) ; 39(6): 986-93, 2015 Jun.
Article en En | MEDLINE | ID: mdl-25771926
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fármacos Antiobesidad / Hormona Liberadora de Prolactina / Lípidos / Obesidad Límite: Animals Idioma: En Revista: Int J Obes (Lond) Asunto de la revista: METABOLISMO Año: 2015 Tipo del documento: Article País de afiliación: República Checa Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fármacos Antiobesidad / Hormona Liberadora de Prolactina / Lípidos / Obesidad Límite: Animals Idioma: En Revista: Int J Obes (Lond) Asunto de la revista: METABOLISMO Año: 2015 Tipo del documento: Article País de afiliación: República Checa Pais de publicación: Reino Unido