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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)
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SYSNO ASEP 0616478 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title 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) Author(s) Peteláková, M. (CZ)
Neprašová, B. (CZ)
Šmotková, Zuzana (FGU-C) ORCID, RID
Myšková, A. (CZ)
Holá, L. (CZ)
Petelák, A. (CZ)
Áčová, A. (CZ)
Cantel, S. (FR)
Fehrentz, J. A. (FR)
Sýkora, D. (CZ)
Kuneš, Jaroslav (FGU-C) RID, ORCID
Železná, B. (CZ)
Maletínská, L. (CZ)Article number 112442 Source Title Molecular and Cellular Endocrinology. - : Elsevier - ISSN 0303-7207
Roč. 597, February (2025)Number of pages 14 s. Language eng - English Country NL - Netherlands Keywords palm-LEAP2(1–14) ; LEAP2 ; ghrelin ; diet-induced obesity ; lipid metabolism ; LEAP2 resistance OECD category Endocrinology and metabolism (including diabetes, hormones) Method of publishing Limited access Institutional support FGU-C - RVO:67985823 UT WOS 001394331700001 EID SCOPUS 85212657866 DOI https://doi.org/10.1016/j.mce.2024.112442 Annotation 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. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2026 Electronic address https://doi.org/10.1016/j.mce.2024.112442
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