Simultaneous treatment with palm-LEAP2(1–14) and feeding high-fat diet attenuates liver lipid metabolism but not obesity: Sign of selective resistance to palm-LEAP2(1–14)

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00603188" target="_blank" >RIV/61388963:_____/25:00603188 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/67985823:_____/25:00616478 RIV/60461373:22340/25:43930206

Výsledek na webu

<a href="https://doi.org/10.1016/j.mce.2024.112442" target="_blank" >https://doi.org/10.1016/j.mce.2024.112442</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.mce.2024.112442" target="_blank" >10.1016/j.mce.2024.112442</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Simultaneous treatment with palm-LEAP2(1–14) and feeding high-fat diet attenuates liver lipid metabolism but not obesity: Sign of selective resistance to palm-LEAP2(1–14)

Popis výsledku v původním jazyce

Liver-enriched antimicrobial peptide 2 (LEAP2) is a natural antagonist/inverse agonist of ghrelin receptor GHSR. Its truncated palmitoylated analog palm-LEAP2(1–14) promised anti-obesity properties because it exhibited favourable stability and an acute anorexigenic effect in our previous studies.Here we demonstrate desirable palm-LEAP2(1–14) pharmacokinetics, with significant levels of the peptide persisting in mouse blood 3 h after its subcutaneous administration. Palm-LEAP2 (1–14) reduced ghrelin-induced c-Fos immunoreactivity in arcuate nucleus and area postrema, in line with previously described silencing of ghrelin orexigenic effect. In spite of this, anti-obesity effect was not reached by two-week palm-LEAP2(1–14) treatment in mice with diet-induced obesity. Similarly, palm-LEAP2(1–14) administered simultaneously with high-fat diet feeding for 8 weeks did not protect mice from development of obesity and related biochemical changes. However, palm-LEAP2(1–14) kept its ability to attenuate liver de novo lipogenesis, and prominently lowered liver gene expression of nuclear receptors PPARG, SREBF1 and PPARA, and also expression of lipogenic and lipolytic enzymes.In our recent study, we described a high-fat diet-induced ghrelin resistance, reversible by switch to standard diet, followed by resistance to the acute anorexigenic effects of palm-LEAP2(1–14). Here we conclude that this resistance to palm-LEAP2(1–14) in obesity is probably selective and does not concern its ability to inhibit liver lipid metabolism.

Název v anglickém jazyce

Simultaneous treatment with palm-LEAP2(1–14) and feeding high-fat diet attenuates liver lipid metabolism but not obesity: Sign of selective resistance to palm-LEAP2(1–14)

Popis výsledku anglicky

Liver-enriched antimicrobial peptide 2 (LEAP2) is a natural antagonist/inverse agonist of ghrelin receptor GHSR. Its truncated palmitoylated analog palm-LEAP2(1–14) promised anti-obesity properties because it exhibited favourable stability and an acute anorexigenic effect in our previous studies.Here we demonstrate desirable palm-LEAP2(1–14) pharmacokinetics, with significant levels of the peptide persisting in mouse blood 3 h after its subcutaneous administration. Palm-LEAP2 (1–14) reduced ghrelin-induced c-Fos immunoreactivity in arcuate nucleus and area postrema, in line with previously described silencing of ghrelin orexigenic effect. In spite of this, anti-obesity effect was not reached by two-week palm-LEAP2(1–14) treatment in mice with diet-induced obesity. Similarly, palm-LEAP2(1–14) administered simultaneously with high-fat diet feeding for 8 weeks did not protect mice from development of obesity and related biochemical changes. However, palm-LEAP2(1–14) kept its ability to attenuate liver de novo lipogenesis, and prominently lowered liver gene expression of nuclear receptors PPARG, SREBF1 and PPARA, and also expression of lipogenic and lipolytic enzymes.In our recent study, we described a high-fat diet-induced ghrelin resistance, reversible by switch to standard diet, followed by resistance to the acute anorexigenic effects of palm-LEAP2(1–14). Here we conclude that this resistance to palm-LEAP2(1–14) in obesity is probably selective and does not concern its ability to inhibit liver lipid metabolism.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30202 - Endocrinology and metabolism (including diabetes, hormones)

Projekt

<a href="/cs/project/GA22-11155S" target="_blank" >GA22-11155S: Vzájemná interakce ghrelinu a jeho nového endogenního antagonisty LEAP2: možná úloha v patologii obezity</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Molecular and Cellular Endocrinology

ISSN

0303-7207

e-ISSN

1872-8057

Svazek periodika

597

Číslo periodika v rámci svazku

February

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

14

Strana od-do

112442

Kód UT WoS článku

001394331700001

EID výsledku v databázi Scopus

2-s2.0-85212657866