Impaired metabolic phenotyping in mice with deletions of GPR10 and NPFFR2 receptors: Implications for lipidized PrRP analog therapy in obesity

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F23%3A00643100" target="_blank" >RIV/61388963:_____/23:00643100 - isvavai.cz</a>

Výsledek na webu

<a href="https://hdl.handle.net/11104/0372943" target="_blank" >https://hdl.handle.net/11104/0372943</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Impaired metabolic phenotyping in mice with deletions of GPR10 and NPFFR2 receptors: Implications for lipidized PrRP analog therapy in obesity

Popis výsledku v původním jazyce

Obesity is a growing global health concern with limited treatment options. Prolactin-releasing peptide (PrRP) is a neuropeptide that can reduce food intake when administered centrally, but loses this effect when given peripherally. However, lipidization of peptides can enhance their stability and efficacy after peripheral administration. Our previous work showed that lipidized PrRP analogs effectively reduced food intake and body weight in mice. PrRP binds to its GPR10 receptor and with high affinity to neuropeptide FF receptor type 2 (NPFFR2), both of which are involved in regulating food intake and energy homeostasis. Palmitoylation of PrRP31 improved its binding and agonist activity for both receptors. In this study, we investigated the metabolic effects of deleting GPR10, NPFFR2, or both receptors in mice. Deletion of GPR10 resulted in increased food intake, elevated insulin levels, impaired glucose tolerance, and altered lipid metabolism gene expression. NPFFR2 deletion led to impaired glucose tolerance on a high-fat diet. Deletion of both GPR10 and NPFFR2 caused sex-specific and diet-dependent metabolic changes, including impaired glucose tolerance and hyperglycemia on a high-fat diet, indicative of prediabetic symptoms. Our findings suggest that targeting GPR10 and NPFFR2 receptors with lipidized PrRP analogs could be a promising therapeutic approach for obesity and related metabolic disorders.nSupported by the project National Institute for Metabolic and Cardiovascular Disease Research (EXCELES Program, ID: LX22NPO5104) - Funded by the European Union - Next Generation EU.

Název v anglickém jazyce

Impaired metabolic phenotyping in mice with deletions of GPR10 and NPFFR2 receptors: Implications for lipidized PrRP analog therapy in obesity

Popis výsledku anglicky

Obesity is a growing global health concern with limited treatment options. Prolactin-releasing peptide (PrRP) is a neuropeptide that can reduce food intake when administered centrally, but loses this effect when given peripherally. However, lipidization of peptides can enhance their stability and efficacy after peripheral administration. Our previous work showed that lipidized PrRP analogs effectively reduced food intake and body weight in mice. PrRP binds to its GPR10 receptor and with high affinity to neuropeptide FF receptor type 2 (NPFFR2), both of which are involved in regulating food intake and energy homeostasis. Palmitoylation of PrRP31 improved its binding and agonist activity for both receptors. In this study, we investigated the metabolic effects of deleting GPR10, NPFFR2, or both receptors in mice. Deletion of GPR10 resulted in increased food intake, elevated insulin levels, impaired glucose tolerance, and altered lipid metabolism gene expression. NPFFR2 deletion led to impaired glucose tolerance on a high-fat diet. Deletion of both GPR10 and NPFFR2 caused sex-specific and diet-dependent metabolic changes, including impaired glucose tolerance and hyperglycemia on a high-fat diet, indicative of prediabetic symptoms. Our findings suggest that targeting GPR10 and NPFFR2 receptors with lipidized PrRP analogs could be a promising therapeutic approach for obesity and related metabolic disorders.nSupported by the project National Institute for Metabolic and Cardiovascular Disease Research (EXCELES Program, ID: LX22NPO5104) - Funded by the European Union - Next Generation EU.

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

2023

Kód důvěrnosti údajů

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