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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
Open accessAbstract
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.
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“neurons in the VTA and/or NAc express GLP-1 (24,25), ghrelin (26,27), leptin (28,29), insulin (30), orexin (31) and melanocortin receptors (32).”
From Obesity and addiction: Neurobiological overlaps (2013) · cites this paper as [24]
In the citing paper
“Moreover, neurons in VTA and/or nucleus accumbens (NAc) express glucagon-like peptide-1 (11,12), ghrelin (13,14), leptin (15,16), insulin (17), orexin (18), and melanocortin receptors (19).”
From The Addictive Dimensionality of Obesity (2013) · cites this paper as [11]
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Research works printed but not linked: 1
- Hayes, 2011, Intracellular signals mediating the food intake suppressive effects of hindbrain glucagon-like-peptide-1 receptor activation., Cell Metab, 13, 320, 10.1016/j.cmet.2011.02.001 · DOI
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Müller, T. D., Finan, B., Bloom, S. R., D'Alessio, D., Drucker, D. J., Flatt, P. R., Fritsche, A., Gribble, F., Grill, H. J., Habener, J. F., et al. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.09.010 · Cited by 1,868
Anti-obesity drug discovery: advances and challenges
Müller, T. D., Blüher, M., Tschöp, M. H., & DiMarchi, R. D. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00337-8 · Cited by 1,021
The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss
Secher, A., Jelsing, J., Baquero, A. F., Hecksher-Sørensen, J., Cowley, M. A., Dalbøge, L. S., Hansen, G., Grove, K. L., Pyke, C., Raun, K., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci75276 · Cited by 961
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Obesity and addiction: Neurobiological overlaps
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Metadata
- Authors
- Alhadeff, A. L., Rupprecht, L. E., & Hayes, M. R.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Hayes, Matthew R.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2012-02-01
- Volume
- 153
- Issue
- 2
- Pages
- 647-658
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC3275387
- OpenAlex
- W2140625608
- Cited by
- 515
- References
- 69
- Citations by year
- 2026: 66 · 2025: 45 · 2024: 38 · 2023: 26 · 2022: 33 · 2021: 36 · 2020: 33 · 2019: 34 · 2018: 25 · 2017: 28 · 2016: 34 · 2015: 31 · 2014: 34 · 2013: 37 · 2012: 13
- FWCI
- 12.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrinology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Pennsylvania
- National Institutes of Health
- U.S. Public Health Service (NIDDK 085435)
- National Institute of Diabetes and Digestive and Kidney Diseases (K01DK085435)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- glucagon-like peptide-1, GLP-1 receptor, nucleus tractus solitarius, ventral tegmental area, nucleus accumbens, mesolimbic reward system, food intake regulation, body weight, palatable food, monosynaptic projection, hindbrain neurons
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Exenatide, Animals, Dose-Response Relationship, Drug, Eating, Gene Expression Regulation, Hypoglycemic Agents, Male, Neurons, Nucleus Accumbens, Peptides, Venoms, Signal Transduction, Rats, Sprague-Dawley, Solitary Nucleus, Ventral Tegmental Area, Receptors, Glucagon, Rats, Glucagon-Like Peptide 1
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