近日，韩国国立首尔大学Hyung Jin Choi等研究人员合作发现，GLP-1通过下丘脑回路增加小鼠和人类的餐前饱腹感。该项研究成果于2024年6月27日在线发表在《科学》杂志上。

研究人员给肥胖症患者服用了GLP-1受体激动剂（GLP-1RA）后，观察到他们的餐前饱腹感增强了。对人类和小鼠大脑样本的分析结果表明，背内侧下丘脑（DMH）中的GLP-1R神经元是编码进食前饱腹感的候选神经元。对DMH^GLP-1R神经元进行光遗传操作可引起饱腹感。钙成像显示，这些神经元积极参与了进食前饱腹感的编码。给予GLP-1RA会在进食行为中选择性地增加DMH^GLP-1R神经元的活性。

研究人员进一步确定了DMH^GLP-1R神经元与弓状NPY/AgRP神经元（ARC^NPY/AgRP）之间错综复杂的相互作用，以调节食物摄入。这些研究结果揭示了GLP-1RA控制进食前饱腹感的下丘脑机制，为肥胖和代谢性疾病提供了新的神经靶点。

据介绍，GLP-1RA是有效的抗肥胖药物。然而，GLP-1RA的确切中枢机制仍然难以捉摸。

附：英文原文

Title: GLP-1 increases preingestive satiation via hypothalamic circuits in mice and humans

Author: Kyu Sik Kim, Joon Seok Park, Eunsang Hwang, Min Jung Park, Hwa Yun Shin, Young Hee Lee, Kyung Min Kim, Laurent Gautron, Elizabeth Godschall, Bryan Portillo, Kyle Grose, Sang-Ho Jung, So Lin Baek, Young Hyun Yun, Doyeon Lee, Eunseong Kim, Jason Ajwani, Seong Ho Yoo, Ali D. Güler, Kevin W. Williams, Hyung Jin Choi

Issue&Volume: 2024-06-27

Abstract: GLP-1 receptor agonists (GLP-1RAs) are effective anti-obesity drugs. However, the precise central mechanisms of GLP-1RAs remain elusive. We administered GLP-1RAs to obese patients and observed heightened sense of preingestive satiation. Analysis of human and mouse brain samples pinpointed GLP-1R neurons in the dorsomedial hypothalamus (DMH) as candidates for encoding preingestive satiation. Optogenetic manipulation of DMHGLP-1R neurons caused satiation. Calcium imaging demonstrated that these neurons are actively involved in encoding preingestive satiation. GLP-1RA administration increased the activity of DMHGLP-1R neurons selectively during eating behavior. We further identified an intricate interplay between DMHGLP-1R neurons and arcuate NPY/AgRP neurons (ARCNPY/AgRP), to regulate food intake. Our findings reveal a hypothalamic mechanism through which GLP-1RAs control preingestive satiation, offering novel neural targets for obesity and metabolic diseases.

DOI: adj2537

Source: https://www.science.org/doi/10.1126/science.adj2537