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

Kód výsledku v 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>

Výsledek na webu

<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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Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/LX22NPO5104" target="_blank" >LX22NPO5104: Národní institut pro výzkum metabolických a kardiovaskulárních onemocnění</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