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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F17%3A00478467" target="_blank" >RIV/61388963:_____/17:00478467 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/67985823:_____/17:00480097 RIV/61388971:_____/17:00478467 RIV/00216208:11110/17:10363393 RIV/00023761:_____/17:N0000020 RIV/00064165:_____/17:10363393

Výsledek na webu

<a href="http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0183449" target="_blank" >http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0183449</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1371/journal.pone.0183449" target="_blank" >10.1371/journal.pone.0183449</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30202 - Endocrinology and metabolism (including diabetes, hormones)

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

PLoS ONE

ISSN

1932-6203

e-ISSN

—

Svazek periodika

12

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

23

Strana od-do

—

Kód UT WoS článku

000408010000024

EID výsledku v databázi Scopus

2-s2.0-85027853200