哥德堡大学Linda Engstrm Ruud研究组在研究中取得进展。他们揭示了半马鲁肽对能量平衡的影响是由迷走背复合体中的Adcyap1⁺神经元介导的。该项研究成果发表在2025年5月22日出版的《细胞—代谢》上。

该课题组人员证明，对semaglutide有反应的迷走神经背侧复合体神经元的再激活模拟了该药物减少食物摄入和体重、促进脂肪利用和条件性味觉厌恶的效果。该课题组研究人员观察到，在瘦小鼠和亚慢性治疗的肥胖小鼠中，许多semaglutide激活区后足区（AP）和孤立束（NTS）神经元的核核表达Adcyap1 mRNA， AP/NTS Adcyap1⁺神经元的消融在很大程度上逆转了semaglutide对能量平衡的影响。Semagulide激活的AP/NTS Adcyap1⁺神经元促进脂肪而不是瘦体重的减少，对条件性味觉厌恶只有适度的影响。

此外，NTS-Adcyap1⁺神经元与表达GLP-1R的AP神经元结合，是信号肽诱导的几种下游饱腹感相关结构激活所必需的。选择性靶向对semaglutide有反应的Adcyap1⁺神经元具有改善未来抗肥胖治疗的潜力。

据了解，GLP-1R激动剂semaglutide的主题是彻底改变肥胖的治疗，但其对能量平衡的机制影响仍然是未知的。

附：英文原文

Title: Semaglutide effects on energy balance are mediated by Adcyap1+ neurons in the dorsal vagal complex

Author: Júlia Teixidor-Deulofeu, Sebastian Blid Skldheden, Ferran Font-Gironès, Andrej Feje, Johan Ruud, Linda Engstrm Ruud

Issue&Volume: 2025-05-22

Abstract: The use of the GLP-1R agonist semaglutide is revolutionizing the treatment of obesity, yet its mechanistic effects on energy balance remain elusive. Here, we demonstrate that reactivation of semaglutide-responsive dorsal vagal complex neurons mimics the drug’s effects of reducing food intake and body weight and promoting fat utilization and conditioned taste aversion. We observe that many of the semaglutide-activated area postrema (AP) and nucleus of the solitary tract (NTS) neurons express Adcyap1 mRNA, and ablation of AP/NTS Adcyap1+ neurons largely reverses semaglutide’s effects on energy balance acutely in lean mice and in subchronically treated obese mice. Semaglutide-activated AP/NTS Adcyap1+ neurons promote the loss of fat rather than lean mass, with only a modest effect on conditioned taste aversion. Furthermore, NTS Adcyap1+ neurons are engaged by GLP-1R-expressing AP neurons and are necessary for semaglutide-induced activation of several downstream satiety-related structures. Selective targeting of semaglutide-responsive Adcyap1+ neurons holds potential for improved future anti-obesity treatments.

DOI: 10.1016/j.cmet.2025.04.018

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(25)00256-6