Veronika Strnadová , Alena Morgan , Magdalena Škrlová , Eliška Haasová , Kristina Bardová , Aneta Myšková , David Sýkora , Jaroslav Kuneš , Blanka Železná , Lenka Maletínská
{"title":"外周给药脂化 NPAF 和 NPFF 类似物不会影响中枢食物摄入调节，但会诱发焦虑样行为","authors":"Veronika Strnadová , Alena Morgan , Magdalena Škrlová , Eliška Haasová , Kristina Bardová , Aneta Myšková , David Sýkora , Jaroslav Kuneš , Blanka Železná , Lenka Maletínská","doi":"10.1016/j.npep.2024.102417","DOIUrl":null,"url":null,"abstract":"<div><p>RF-amide peptides influence multiple physiological processes, including the regulation of appetite, stress responses, behavior, and reproductive and endocrine functions. In this study, we examined the roles of neuropeptide FF receptors (NPFFR1 and NPFFR2) by generating several lipidized analogs of neuropeptide AF (NPAF) and 1DMe, a stable analog of neuropeptide FF (NPFF). These analogs were administered peripherally for the first time to investigate their effects on food intake and other potential physiological outcomes. Lipidized NPAF and 1DMe analogs exhibited enhanced stability and increased pharmacokinetics. These analogs demonstrated preserved high affinity for NPFFR2 in the nanomolar range, while the binding affinity for NPFFR1 was tens of nanomoles. They activated the ERK and Akt signaling pathways in cells overexpressing the NPFFR1 and NPFFR2 receptors.</p><p>Acute food intake in fasted mice decreased after the peripheral administration of oct-NPAF or oct-1DMe. However, this effect was not as pronounced as that observed after the injection of palm<sup>11</sup>-PrRP31, a potent anorexigenic compound used as a comparator that binds to GPR10 and the NPFFR2 receptor with high affinity. Neither oct-1DMe nor oct-NPAF decreased food intake or body weight in mice with diet-induced obesity during long-term treatment. In mice treated with oct-1DMe, we observed decreased activity in the central zone during the open field test and decreased activity in the open arms of the elevated plus maze. Furthermore, we observed a decrease in plasma noradrenaline levels and an increase in plasma corticosterone levels, as well as an increase in <em>Crh</em> expression in the hypothalamus. Moreover, neuronal activity in the hypothalamus was increased after treatment with oct-1DMe.</p><p>In this study, we report that oct-1DMe did not have any long-term effects on the central regulation of food intake; however, it caused anxiety-like behavior.</p></div>","PeriodicalId":19254,"journal":{"name":"Neuropeptides","volume":null,"pages":null},"PeriodicalIF":2.5000,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0143417924000167/pdfft?md5=d8c7a303e8855876aba893145ad60858&pid=1-s2.0-S0143417924000167-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Peripheral administration of lipidized NPAF and NPFF analogs does not influence central food intake regulation but induces anxiety-like behavior\",\"authors\":\"Veronika Strnadová , Alena Morgan , Magdalena Škrlová , Eliška Haasová , Kristina Bardová , Aneta Myšková , David Sýkora , Jaroslav Kuneš , Blanka Železná , Lenka Maletínská\",\"doi\":\"10.1016/j.npep.2024.102417\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>RF-amide peptides influence multiple physiological processes, including the regulation of appetite, stress responses, behavior, and reproductive and endocrine functions. In this study, we examined the roles of neuropeptide FF receptors (NPFFR1 and NPFFR2) by generating several lipidized analogs of neuropeptide AF (NPAF) and 1DMe, a stable analog of neuropeptide FF (NPFF). These analogs were administered peripherally for the first time to investigate their effects on food intake and other potential physiological outcomes. Lipidized NPAF and 1DMe analogs exhibited enhanced stability and increased pharmacokinetics. These analogs demonstrated preserved high affinity for NPFFR2 in the nanomolar range, while the binding affinity for NPFFR1 was tens of nanomoles. They activated the ERK and Akt signaling pathways in cells overexpressing the NPFFR1 and NPFFR2 receptors.</p><p>Acute food intake in fasted mice decreased after the peripheral administration of oct-NPAF or oct-1DMe. However, this effect was not as pronounced as that observed after the injection of palm<sup>11</sup>-PrRP31, a potent anorexigenic compound used as a comparator that binds to GPR10 and the NPFFR2 receptor with high affinity. Neither oct-1DMe nor oct-NPAF decreased food intake or body weight in mice with diet-induced obesity during long-term treatment. In mice treated with oct-1DMe, we observed decreased activity in the central zone during the open field test and decreased activity in the open arms of the elevated plus maze. Furthermore, we observed a decrease in plasma noradrenaline levels and an increase in plasma corticosterone levels, as well as an increase in <em>Crh</em> expression in the hypothalamus. 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Peripheral administration of lipidized NPAF and NPFF analogs does not influence central food intake regulation but induces anxiety-like behavior
RF-amide peptides influence multiple physiological processes, including the regulation of appetite, stress responses, behavior, and reproductive and endocrine functions. In this study, we examined the roles of neuropeptide FF receptors (NPFFR1 and NPFFR2) by generating several lipidized analogs of neuropeptide AF (NPAF) and 1DMe, a stable analog of neuropeptide FF (NPFF). These analogs were administered peripherally for the first time to investigate their effects on food intake and other potential physiological outcomes. Lipidized NPAF and 1DMe analogs exhibited enhanced stability and increased pharmacokinetics. These analogs demonstrated preserved high affinity for NPFFR2 in the nanomolar range, while the binding affinity for NPFFR1 was tens of nanomoles. They activated the ERK and Akt signaling pathways in cells overexpressing the NPFFR1 and NPFFR2 receptors.
Acute food intake in fasted mice decreased after the peripheral administration of oct-NPAF or oct-1DMe. However, this effect was not as pronounced as that observed after the injection of palm11-PrRP31, a potent anorexigenic compound used as a comparator that binds to GPR10 and the NPFFR2 receptor with high affinity. Neither oct-1DMe nor oct-NPAF decreased food intake or body weight in mice with diet-induced obesity during long-term treatment. In mice treated with oct-1DMe, we observed decreased activity in the central zone during the open field test and decreased activity in the open arms of the elevated plus maze. Furthermore, we observed a decrease in plasma noradrenaline levels and an increase in plasma corticosterone levels, as well as an increase in Crh expression in the hypothalamus. Moreover, neuronal activity in the hypothalamus was increased after treatment with oct-1DMe.
In this study, we report that oct-1DMe did not have any long-term effects on the central regulation of food intake; however, it caused anxiety-like behavior.
期刊介绍：
The aim of Neuropeptides is the rapid publication of original research and review articles, dealing with the structure, distribution, actions and functions of peptides in the central and peripheral nervous systems. The explosion of research activity in this field has led to the identification of numerous naturally occurring endogenous peptides which act as neurotransmitters, neuromodulators, or trophic factors, to mediate nervous system functions. Increasing numbers of non-peptide ligands of neuropeptide receptors have been developed, which act as agonists or antagonists in peptidergic systems.
The journal provides a unique opportunity of integrating the many disciplines involved in all neuropeptide research. The journal publishes articles on all aspects of the neuropeptide field, with particular emphasis on gene regulation of peptide expression, peptide receptor subtypes, transgenic and knockout mice with mutations in genes for neuropeptides and peptide receptors, neuroanatomy, physiology, behaviour, neurotrophic factors, preclinical drug evaluation, clinical studies, and clinical trials.
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