Lipidized prolactin-releasing peptide analogs: From structure to function in obesity treatment

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00638938" target="_blank" >RIV/61388963:_____/25:00638938 - isvavai.cz</a>

Result on the web

<a href="https://hdl.handle.net/11104/0369487" target="_blank" >https://hdl.handle.net/11104/0369487</a>

DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Lipidized prolactin-releasing peptide analogs: From structure to function in obesity treatment

Original language description

Obesity is a growing global health challenge, yet effective long-term pharmacotherapy remains limited. Prolactin-releasing peptide (PrRP) is a promising anorexigenic neuropeptide, but its clinical application is limited by stability and ability to cross the blood–brain barrier. To overcome these limitations, our laboratory developed lipidized PrRP analogs, such as palm¹¹ PrRP31, which can reduce food intake and body weight even after peripheral administration. Lipidized PrRP analogs exhibit enhanced stability and increased binding affinity toward both GPR10 (PRLHR), the canonical PrRP receptor, and neuropeptide FF receptor type 2 (NPFFR2/GPR74), which is involved in energy homeostasis and thermogenesis.nTo elucidate the mechanism of action of lipidized PrRP analogs, we employed knockout (KO) mice lacking GPR10, NPFFR2, or both receptors. GPR10 KO mice exhibited increased adiposity, hyperleptinemia, hyperinsulinemia, and impaired glucose tolerance, indicating a key role in regulating energy and glucose metabolism. NPFFR2 KO mice displayed a lean phenotype but developed marked glucose intolerance, particularly under high-fat diet conditions. Deletion of both GPR10 and NPFFR2 (double KO mice) resulted in sex-specific metabolic disturbances, including late-onset obesity, insulin resistance, and impaired glucose tolerance.nChronic treatment with palm¹¹ PrRP31 decreased food intake and body weight in wild-type mice as well as in single-receptor KO mice, but had no effect in double KO mice, confirming the necessity of both receptors for full anti-obesity effect. These findings highlight the therapeutic potential of lipidized PrRP analogs and support the dual targeting of GPR10 and NPFFR2 as a promising strategy for the treatment of obesity.n

Czech name

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Czech description

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Type

O - Miscellaneous

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

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