Ozempic通过激活饥饿神经元维持减肥效果

耶鲁大学的研究发现，Ozempic（semaglutide）在大脑中的作用机制与科学界原有认识相悖 1。这种GLP-1类药物并非通过抑制与饥饿相关的AgRP神经元来发挥作用，反而激活了这些神经元 1。

研究人员在小鼠模型中进行了实验，在缺乏AgRP神经元的转基因小鼠中，GLP-1药物无法维持体重减轻 1。这进一步证实了这些神经元对维持脂肪减少的重要性 1。临床上，Ozempic能够产生10至15%或更多的持续体重减轻 1。

这项研究由耶鲁神经科学博士候选人Mateus d'Ávila领导 1，相关成果已于2026年8月发表在《美国国家科学院院刊》第123卷第32期上 1，为开发更有效的肥胖症药物提供了新的生物学靶点 1。

Researchers at Yale University have discovered that semaglutide, the active ingredient in Ozempic, operates through a counterintuitive mechanism in the brain 1. Rather than suppressing hunger-related neurons as previously thought, the drug actually activates AgRP neurons, which are essential for sustaining weight loss 1. This finding challenges conventional understanding of how the medication works at the neurological level.

The research team, led by doctoral candidate Mateus d'Ávila, conducted experiments using transgenic mice lacking AgRP neurons to test their hypothesis 1. When these modified mice were treated with GLP-1 drugs, the medications failed to maintain weight reduction, demonstrating the critical role these neurons play in the drug's effectiveness 1. The study provides evidence that AgRP neuron activation, rather than inhibition, underpins the mechanism by which Ozempic produces sustained weight loss of 10-15 percent or greater 1.

The findings have been published in the August 2026 issue of the Proceedings of the National Academy of Sciences, Volume 123, Issue 32 1. By identifying this unexpected biological pathway, the research opens new directions for developing more effective obesity treatments targeting these specific neural mechanisms 1.