title: Palmitoylated PrRP analog decreases body weight in DIO rats but not in ZDF rats.
abstract: Anorexigenic neuropeptides produced and acting in the brain have the potential to decrease food intake and ameliorate obesity, but are ineffective after peripheral application, owing to a limited ability to cross the blood-brain barrier. 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-knockout and Prrp receptor-knockout mice. The aim of this study was to characterize the subchronic effect of a palmitoylated PrRP analog in two rat models of obesity and diabetes: diet-induced obese Sprague-Dawley rats and leptin receptor-deficient Zucker diabetic (ZDF) rats. In the rats with diet-induced obesity (DIO), a two-week intraperitoneal treatment with palmitoylated PrRP lowered food intake by 24% and body weight by 8%. This treatment also improved glucose tolerance and tended to decrease leptin levels and adipose tissue masses in a dose-dependent manner. In contrast, in ZDF rats, the same treatment with palmitoylated PrRP lowered food intake but did not significantly affect body weight or glucose tolerance, probably in consequence of severe leptin resistance due to a nonfunctional leptin receptor. Our data indicate a good efficacy of lipidized PrRP in DIO rats. Thus, the strong anorexigenic, body weight-reducing, and glucose tolerance-improving effects make palmitoylated PrRP an attractive candidate for anti-obesity treatment.
authors.affiliation: Institute of Organic Chemistry and BiochemistryAcademy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Holubová
authors.affiliation: Institute of Organic Chemistry and BiochemistryAcademy of Sciences of the Czech Republic, Prague, Czech Republic Department of Analytical ChemistryUniversity of Chemistry and Technology, Prague, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Zemenová
authors.affiliation: Institute of Organic Chemistry and BiochemistryAcademy of Sciences of the Czech Republic, Prague, Czech Republic Institute of PhysiologyAcademy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Barbora
authors.initials: B
authors.lastname: Mikulášková
authors.affiliation: Apigenex LimitedPrague, Czech Republic.
authors.forename: Vladimíra
authors.initials: V
authors.lastname: Panajotova
authors.affiliation: Apigenex LimitedPrague, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Stöhr
authors.affiliation: First Faculty of MedicineCharles University, Prague, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Haluzík
authors.affiliation: Institute of Organic Chemistry and BiochemistryAcademy of Sciences of the Czech Republic, Prague, Czech Republic Institute of PhysiologyAcademy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Kuneš
authors.affiliation: Institute of Organic Chemistry and BiochemistryAcademy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Blanka
authors.initials: B
authors.lastname: Železná
authors.affiliation: Institute of Organic Chemistry and BiochemistryAcademy of Sciences of the Czech Republic, Prague, Czech Republic maletin@uochb.cas.cz.
authors.forename: Lenka
authors.initials: L
authors.lastname: Maletínská
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D015195:Drug Design; D004435:Eating / Q000187:drug effects; D005951:Glucose Tolerance Test; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D054878:Lipoylation; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D056690:Prolactin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D054411:Receptors, Leptin / Q000172:deficiency
chemical_list: D001067:Appetite Depressants; D056690:Prolactin-Releasing Hormone; D012333:RNA, Messenger; D054411:Receptors, Leptin
keywords: ZDF rats; diet-induced obesity; food intake; lipidization; prolactin-releasing peptide; rat