Stable lipidized analogs of neuropeptides for treatment of obesity and type 2 diabetes

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00641781" target="_blank" >RIV/61388963:_____/25:00641781 - isvavai.cz</a>

Result on the web

<a href="https://hdl.handle.net/11104/0371816" target="_blank" >https://hdl.handle.net/11104/0371816</a>

DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Stable lipidized analogs of neuropeptides for treatment of obesity and type 2 diabetes

Original language description

Recently discovered anorexigenic neuropeptides, such as prolactin-releasing peptide (PrRP) and cocaine- and amphetamine-regulated transcript (CART) peptide, as well as antagonist/inverse agonist of ghrelin receptor represent new trends in development of anti-obesity agents. Neuropeptides are released and acting directly in brain areas regulating food intake, but generally do not cross the blood-brain barrier if administered peripherally. We succeeded to design stable lipidized PrRP and CART peptide analogs with prolonged acute anorexigenic effect after peripheral administration in mice and rats. Repeated peripheral administration of the lipidized analogs resulted in long-lasting anti-obesity and antidiabetic effects in rodent models of diet induced obesity and insulin resistance. Besides anorexigenic peptides, also antagonists and inverse agonists of peripherally released and centrally acting orexigenic peptide ghrelin are candidates for anti-obesity treatment. Recently, liver- enriched antimicrobial peptide (LEAP2) as an endogenous ghrelin antagonist/ inverse agonist was discovered and we explore its possible role in organism as well as anti-obesity properties of newly designed shortened LEAP2 analogs lipidized at C-terminus. These analogs showed high affinity to ghrelin receptor and antagonistic/inverse agonistic features when antagonizing orexigenic effect of ghrelin in mice. Moreover, repeated peripheral administration of palmitoylated LEAP2 analog showed strong anti-obesity effect in mouse model of postmenopausal obesity. We showed that lipidization of anorexigenic peptides might be an effective way to transmit the desired effect to the central nervous system after peripheral administration in preclinical rodent models, for a potential treatment of obesity and related complications such as Type 2 diabetes.

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

<a href="/en/project/LX22NPO5104" target="_blank" >LX22NPO5104: National Institute for Research of Metabolic and Cardiovascular Diseases</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