Impact of novel palmitoylated prolactin-releasing peptide analogs on metabolic changes in mice with diet-induced obesity

0478467 - ÚOCHB 2018 RIV US eng J - Článek v odborném periodiku
Pražienková, Veronika - Holubová, Martina - Pelantová, Helena - Bugáňová, Martina - Pirník, Z. - Mikulášková, Barbora - Popelová, Andrea - Blechová, Miroslava - Haluzík, M. - Železná, Blanka - Kuzma, Marek - Kuneš, Jaroslav - Maletínská, Lenka
Impact of novel palmitoylated prolactin-releasing peptide analogs on metabolic changes in mice with diet-induced obesity.
PLoS ONE. Roč. 12, č. 8 (2017), č. článku e0183449. ISSN 1932-6203. E-ISSN 1932-6203
Grant CEP: GA ČR(CZ) GA15-08679S; GA ČR GA13-14105S
Institucionální podpora: RVO:61388963 ; RVO:61388971
Klíčová slova: food intake regulation * peroxisome proliferation * lipidized analogs
Obor OECD: Endocrinology and metabolism (including diabetes, hormones)
Impakt faktor: 2.766, rok: 2017
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0183449

Analogs of anorexigenic neuropeptides, such as prolactin-releasing peptide ( PrRP), have a potential as new anti-obesity drugs. In our previous study, palmitic acid attached to the N-erminus of PrRP enabled its central anorexigenic effects after peripheral administration. In this study, two linkers, gamma-glutamic acid at Lys(11) and a short, modified polyethylene glycol at the N-terminal Ser and/or Lys(11), were applied for the palmitoylation of PrRP31 to improve its bioavailability. These analogs had a high affinity and activation ability to the PrRP receptor GPR10 and the neuropeptide FF2 receptor, as well as short-term anorexigenic effect similar to PrRP palmitoylated at the N-terminus. Two-week treatment with analogs that were palmitoylated through linkers to Lys(11) (analogs 1 and 2), but not with analog modified both at the N-terminus and Lys(11) (analog 3) decreased body and liver weights, insulin, leptin, triglyceride, cholesterol and free fatty acid plasma levels in a mouse model of diet-induced obesity. Moreover, the expression of uncoupling protein-1 was increased in brown fat suggesting an increase in energy expenditure. In addition, treatment with analogs 1 and 2 but not analog 3 significantly decreased urinary concentrations of 1-methylnicotinamide and its oxidation products N-methyl-2-pyridone-5-carboxamide and N-methyl-4-pyridone-3-carboxamide, as shown by NMR-based metabolomics. This observation confirmed the previously reported increase in nicotinamide derivatives in obesity and type 2 diabetes mellitus and the effectiveness of analogs 1 and 2 in the treatment of these disorders.
Trvalý link: http://hdl.handle.net/11104/0274585