Hwang Eunsang, Portillo Bryan, Williams Kevin W
Center for Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
Endocrinology. 2025 Sep 8;166(10). doi: 10.1210/endocr/bqaf125.
Hypothalamic nuclei, including the arcuate nucleus, the paraventricular hypothalamic area, and the dorsomedial hypothalamus, integrate glucagon-like peptide-1 (GLP-1) signals to regulate feeding behavior, body weight, and glucose homeostasis. Recent advances have revealed that both endogenous GLP-1, produced by preproglucagon neurons in the nucleus tractus solitarius, and pharmacological GLP-1 receptor agonists (GLP-1RAs) engage distinct and overlapping hypothalamic circuits. However, the mechanisms underlying these effects involve circuit redundancy, diverse modes of signal integration, and context-dependent actions of different GLP-1R ligands. In this review, we propose a conceptual framework highlighting opportunities for future research and the therapeutic potential of targeting central GLP-1 pathways for obesity treatment.
下丘脑核团，包括弓状核、下丘脑室旁区和下丘脑背内侧核，整合胰高血糖素样肽-1（GLP-1）信号以调节摄食行为、体重和葡萄糖稳态。最近的进展表明，孤束核中前胰高血糖素神经元产生的内源性GLP-1和药理GLP-1受体激动剂（GLP-1RAs）均参与不同但重叠的下丘脑回路。然而，这些效应背后的机制涉及回路冗余、多种信号整合模式以及不同GLP-1R配体的情境依赖性作用。在本综述中，我们提出了一个概念框架，突出了未来研究的机会以及靶向中枢GLP-1通路治疗肥胖症的治疗潜力。
