Glucagon-Like Peptide 1 (GLP-1) Action on Hypothalamic Feeding Circuits

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.