催乳素释放肽类似物主要通过持续的脂肪酸氧化而不是吞咽来减轻体重，这一成果由英国曼彻斯特大学Simon M. Luckman课题组经过不懈努力而取得。相关论文于2025年12月1日发表在《细胞—代谢》杂志上。

该团队描述了一种修饰肽NN501，具有GPR10和神经肽FF受体2 （NPFFR2）的激动剂特性，在全身给药时可以减轻体重，而不会引起明显的厌恶反应。减肥效果与胰高血糖素样肽1 （GLP-1）受体激动剂相似，但对食物摄入的影响不大，提示其减肥机制不同。

此外，当停止治疗时，接受NN501的小鼠表现出更缓慢的体重恢复，没有代偿性贪食反应（如热量限制和GLP-1受体激动作用所观察到的）。相反，NN501增加了治疗过程中的能量消耗，并对脂肪酸氧化有持续的影响。这些结果表明GPR10/NPFFR2激动作用通过GLP-1受体激动作用的替代机制产生体重减轻，表明它可能是肥胖的可行替代或补充疗法。

据了解，催乳素释放肽及其同源受体G蛋白偶联受体（GPR）10在啮齿动物和人类的体重生理调节中都起重要作用。

附：英文原文

Title: Analog of prolactin-releasing peptide reduces body weight primarily through sustained fatty acid oxidation rather than hypophagia

Author: Claire H. Feetham, Sam Groom, Linu M. John, Berit Ostergaard Christoffersen, Valeria Collabolletta, David Lyons, Antony Adamson, Sofia Lundh, Marina Kjrgaard Gerstenberg, Mads Tang-Christensen, Kilian W. Conde-Frieboes, Anna Secher, Ann Maria Kruse Hansen, Simon M. Luckman

Issue&Volume: 2025-12-01

Abstract: Prolactin-releasing peptide and its cognate receptor, G protein-coupled receptor (GPR)10, are important in the physiological regulation of body weight in both rodents and humans. Here, we describe a modified peptide, NN501, with agonist properties at both GPR10 and neuropeptide FF receptor 2 (NPFFR2), which reduces body weight when administered systemically without causing obvious aversive responses. Weight reduction is similar to that of glucagon-like peptide 1 (GLP-1) receptor agonists, but with only a modest effect on food intake, suggesting a different weight-lowering mechanism. Moreover, when treatment is discontinued, mice receiving NN501 display a more gradual weight regain and no compensatory hyperphagic response (as is observed with caloric restriction and GLP-1 receptor agonism). Instead, NN501 increases energy expenditure on treatment and has a sustained effect on fatty-acid oxidation. These results indicate that GPR10/NPFFR2 agonism produces weight loss by alternative mechanisms to GLP-1 receptor agonism, suggesting it could be a viable alternative or complementary therapy for obesity.

DOI: 10.1016/j.cmet.2025.10.021

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(25)00481-4