Lipidized analogues of the anorexigenic CART (cocaine- and amphetamine-regulated transcript) neuropeptide show anorexigenic and neuroprotective potential in mouse model of monosodium-glutamate induced obesity

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22340%2F24%3A43930078" target="_blank" >RIV/60461373:22340/24:43930078 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/67985823:_____/24:00597744 RIV/61388963:_____/24:00588424 RIV/00216208:11110/24:10483752

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0014299924005533?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0014299924005533?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejphar.2024.176864" target="_blank" >10.1016/j.ejphar.2024.176864</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Lipidized analogues of the anorexigenic CART (cocaine- and amphetamine-regulated transcript) neuropeptide show anorexigenic and neuroprotective potential in mouse model of monosodium-glutamate induced obesity

Popis výsledku v původním jazyce

Aims: This study investigates the neuroprotective effects of lipidized analogues of 2-SS-CART(61-102) derived from anorexigenic neuropeptide cocaine- and amphetamine-regulated transcript peptide (CARTp) in light of the link between obesity, its comorbidities, and the development of Alzheimer&apos;s disease. Methods: We introduce novel lipidized analogues derived from 2-SS-CART(61-102), a specific analogue of natural CART(61-102), with two disulfide bridges. Using hypothermic PC12 cells, we tested the effect of the most potent analogues on Tau phosphorylation. We further described the anorexigenic and neuroprotective potential of subcutaneously (SC) injected lipidized CARTp analogue in a mouse model with prediabetes and obesity induced by neonatal monosodium glutamate (MSG) administration. Results: Compared to the non-lipidized 2-SS-CART(61-102), all lipidized analogues exhibited a potent binding affinity to PC12 cells and enhanced in vitro stability in rat plasma. Two most potent lipidized analogues attenuated hypothermia-induced Tau hyperphosphorylation at multiple epitopes. Subsequently, chronic SC treatment with palm-2-SS-CART(61-102) significantly decreased body weight and food intake, improved metabolic parameters, decreased level of pTau and increased neurogenesis in hippocampi of obese MSG mice. Conclusion: Our unique CARTp analogue palm-2-SS-CART(61-102) shows promise as a potent anti-obesity and neuroprotective agent.

Název v anglickém jazyce

Lipidized analogues of the anorexigenic CART (cocaine- and amphetamine-regulated transcript) neuropeptide show anorexigenic and neuroprotective potential in mouse model of monosodium-glutamate induced obesity

Popis výsledku anglicky

Aims: This study investigates the neuroprotective effects of lipidized analogues of 2-SS-CART(61-102) derived from anorexigenic neuropeptide cocaine- and amphetamine-regulated transcript peptide (CARTp) in light of the link between obesity, its comorbidities, and the development of Alzheimer&apos;s disease. Methods: We introduce novel lipidized analogues derived from 2-SS-CART(61-102), a specific analogue of natural CART(61-102), with two disulfide bridges. Using hypothermic PC12 cells, we tested the effect of the most potent analogues on Tau phosphorylation. We further described the anorexigenic and neuroprotective potential of subcutaneously (SC) injected lipidized CARTp analogue in a mouse model with prediabetes and obesity induced by neonatal monosodium glutamate (MSG) administration. Results: Compared to the non-lipidized 2-SS-CART(61-102), all lipidized analogues exhibited a potent binding affinity to PC12 cells and enhanced in vitro stability in rat plasma. Two most potent lipidized analogues attenuated hypothermia-induced Tau hyperphosphorylation at multiple epitopes. Subsequently, chronic SC treatment with palm-2-SS-CART(61-102) significantly decreased body weight and food intake, improved metabolic parameters, decreased level of pTau and increased neurogenesis in hippocampi of obese MSG mice. Conclusion: Our unique CARTp analogue palm-2-SS-CART(61-102) shows promise as a potent anti-obesity and neuroprotective agent.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

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

2024

Kód důvěrnosti údajů

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

Název periodika

European Journal of Pharmacology

ISSN

0014-2999

e-ISSN

1879-0712

Svazek periodika

980

Číslo periodika v rámci svazku

5 October 2024

Stát vydavatele periodika

ZA - Jihoafrická republika

Počet stran výsledku

13

Strana od-do

—

Kód UT WoS článku

001290922300001

EID výsledku v databázi Scopus

2-s2.0-85200422000