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.

中文翻译：

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脂质化 NPAF 和 NPFF 类似物的外周给药不会影响中枢食物摄入调节，但会诱发焦虑样行为

RF-酰胺肽影响多种生理过程，包括食欲调节、应激反应、行为以及生殖和内分泌功能。在这项研究中，我们通过生成神经肽 AF (NPAF) 的几种脂质化类似物和 1DMe（神经肽 FF (NPFF) 的稳定类似物）来检查神经肽 FF 受体（NPFFR1 和 NPFFR2）的作用。这些类似物首次在外周给药，以研究它们对食物摄入和其他潜在生理结果的影响。脂质化 NPAF 和 1DMe 类似物表现出增强的稳定性和增强的药代动力学。这些类似物对 NPFFR2 保持了纳摩尔范围内的高亲和力，而对 NPFFR1 的结合亲和力为数十纳摩尔。他们激活了过度表达 NPFFR1 和 NPFFR2 受体的细胞中的 ERK 和 Akt 信号通路。