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)

Result code in 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>

Alternative codes found

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

Result on the web

<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>

Result language

angličtina

Original language name

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)

Original language description

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.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30202 - Endocrinology and metabolism (including diabetes, hormones)

Project

<a href="/en/project/GA22-11155S" target="_blank" >GA22-11155S: Interplay between ghrelin and its novel endogenous antagonist LEAP2: possible role in the pathology of obesity</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

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

Name of the periodical

Molecular and Cellular Endocrinology

ISSN

0303-7207

e-ISSN

1872-8057

Volume of the periodical

597

Issue of the periodical within the volume

February

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

14

Pages from-to

112442

UT code for WoS article

001394331700001

EID of the result in the Scopus database

2-s2.0-85212657866