GLP-1 Neurons in the Nucleus of the Solitary Tract Project Directly to the Ventral Tegmental Area and Nucleus Accumbens to Control for Food Intake
Overview
Affiliations
Central glucagon-like-peptide-1 (GLP-1) receptor activation reduces food intake; however, brain nuclei and mechanism(s) mediating this effect remain poorly understood. Although central nervous system GLP-1 is produced almost exclusively in the nucleus of the solitary tract in the hindbrain, GLP-1 receptors (GLP-1R) are expressed throughout the brain, including nuclei in the mesolimbic reward system (MRS), e.g. the ventral tegmental area (VTA) and the nucleus accumbens (NAc). Here, we examine the MRS as a potential site of action for GLP-1-mediated control of food intake and body weight. Double immunohistochemistry for Fluorogold (monosynaptic retrograde tracer) and GLP-1 neuron immunoreactivity indicated that GLP-1-producing nucleus tractus solitarius neurons project directly to the VTA, the NAc core, and the NAc shell. Pharmacological data showed that GLP-1R activation in the VTA, NAc core, and NAc shell decreased food intake, especially of highly-palatable foods, and body weight. Moreover, blockade of endogenous GLP-1R signaling in the VTA and NAc core resulted in a significant increase in food intake, establishing a physiological relevance for GLP-1 signaling in the MRS. Current data highlight these nuclei within the MRS as novel sites for GLP-1R-mediated control of food intake and body weight.
Merkel R, Hernandez N, Weir V, Zhang Y, Caffrey A, Rich M Sci Adv. 2025; 11(9):eadr5051.
PMID: 40009667 PMC: 11864183. DOI: 10.1126/sciadv.adr5051.
Use of semaglutide in a 54-year-old patient with cocaine abuse and weight loss: a case report.
Romeo V J Med Case Rep. 2025; 19(1):57.
PMID: 39962582 PMC: 11834608. DOI: 10.1186/s13256-025-05049-w.
Effects of GLP-1 Receptor Agonists in Alcohol Use Disorder.
Klausen M, Knudsen G, Vilsboll T, Fink-Jensen A Basic Clin Pharmacol Toxicol. 2025; 136(3):e70004.
PMID: 39891507 PMC: 11786240. DOI: 10.1111/bcpt.70004.
Integration of Glucagon-Like Peptide 1 Receptor Actions Through the Central Amygdala.
Duran M, Willis J, Dalvi N, Fokakis Z, Virkus S, Hardaway J Endocrinology. 2025; 166(3).
PMID: 39888375 PMC: 11850305. DOI: 10.1210/endocr/bqaf019.
Glucagon-Like Peptide-1 Links Ingestion, Homeostasis, and the Heart.
Krieger J, Daniels D, Lee S, Mastitskaya S, Langhans W Compr Physiol. 2025; 15(1):e7.
PMID: 39887844 PMC: 11790259. DOI: 10.1002/cph4.7.