Role of the glucagon-like-peptide-1 receptor in the control of energy balance
Open accessAbstract
The peripheral and central glucagon-like-peptide-1 (GLP-1) systems play an essential role in glycemic and energy balance regulation. Thus, pharmacological targeting of peripheral and/or central GLP-1 receptors (GLP-1R) may represent a potential long-term treatment option for both obesity and type-II diabetes mellitus (T2DM). Uncovering and understanding the neural pathways, physiological mechanisms, specific GLP-1R populations, and intracellular signaling cascades that mediate the food intake inhibitory and incretin effects produced by GLP-1R activation are vital to the development of these potential successful therapeutics. Particular focus will be given to the essential role of the nucleus tractus solitarius (NTS) in the caudal brainstem, as well as the gut-to-brain communication by vagal afferent fibers in mediating the physiological and behavioral responses following GLP-1R activation. The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009.
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GLP-1R expression in key reward- and stress-related brain regions may contribute to food and alcohol seeking and consumption.
“GLP-1R expression in these key reward- and stress-related brain regions may contribute to food (24-27) and alcohol (28–30) seeking and consumption.”
From The glucagon-like peptide-1 (GLP-1) analogue semaglutide reduces alcohol drinking and modulates central GABA neurotransmission (2023) · cites this paper as [24]
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The GLP-1 agonist exendin-4 reduces food intake in nonhuman primates through changes in meal size
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T1r3 and α‐Gustducin in Gut Regulate Secretion of Glucagon‐like Peptide‐1
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Sensory nerves contribute to insulin secretion by glucagon-like peptide-1 in mice
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Brain-adipose tissue neural crosstalk
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Sensory mechanisms: transmitters, modulators and reflexes
Raybould, H. E., Cooke, H. J., & Christofi, F. L. (2004) · Neurogastroenterology & Motility · doi:10.1111/j.1743-3150.2004.00477.x · Cited by 90 · see citing works
Chaudhri, O. B., Parkinson, J. R. C., Kuo, Y., Druce, M. R., Herlihy, A. H., Bell, J. D., Dhillo, W. S., Stanley, S. A., Ghatei, M. A., & Bloom, S. R. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.09.033 · Cited by 87 · see citing works
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Self-citationComparison of weight loss and body composition changes with four surgical procedures
Strain, G. W., Gagner, M., Pomp, A., Dakin, G. F., Inabnet, W. B., Hsieh, J., Heacock, L. C., & Christos, P. J. (2009) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2009.04.001 · Cited by 87 · see citing works
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Gut Peptide Signaling in the Controls of Food Intake
Moran, T. H. (2006) · Obesity · doi:10.1038/oby.2006.318 · Cited by 81 · see citing works
Glucagon-like peptide-1 excites pancreas-projecting preganglionic vagal motoneurons
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Role of the incretin pathway in the pathogenesis of type 2 diabetes mellitus
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Effect of Leptin on Hypothalamic GLP-1 Peptide and Brain-Stem Pre-proglucagon mRNA
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Hayes, M. R., & Covașă, M. (2006) · Brain Research · doi:10.1016/j.brainres.2006.03.018 · Cited by 46 · see citing works
Self-citationBaraboi, E., Smith, P., Ferguson, A. V., & Richard, D. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00326.2009 · Cited by 46 · see citing works
Bojanowska, E., & Nowak, A. (2007) · PubMed · Cited by 40 · see citing works
Leptin: Taking the Path Less Traveled
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Merchenthaler (1999) · doi:10.1002/(sici)1096-9861(19990111)403:2
Flagged first, then by citations
Research works printed but not linked: 5
- [16]Hayes MR Skibicka KP Grill HJ Caudal brainstem processing is sufficient for behavioral, sympathetic, and parasympathetic responses driven by peripheral and hindbrain glucagon-like-peptide-1 receptor stimulation Endocrinology 2008 149 8 4059 68 18420740 PMC2488211
- [53]Ruttimann EB Intrameal Hepatic-Portal and Intraperitoneal Infusions of Glucagon-Like Peptide-1 (GLP-1) Reduce Spontaneous Meal Size in the Rat via Different Mechanisms Endocrinology 2008 PMC2654737 18948395
- [61]Sarwer DB The Management of Mood Disorders with Anti-depressant Medications After Bariatric Surgery Current Psychiatry 2010 In Press
- [87]Hayes MR Bradley L Grill HJ Endogenous hindbrain GLP-1 receptor activation contributes to the control of food intake by mediating gastric satiation signaling Endocrinology 2009 In Press PMC2689794 19264875
- [111]Grill HJ Hayes MR The nucleus tractus solitarius: a portal for visceral afferent signal processing, energy status assessment and integration of their combined effects on food intake Int J Obes (Lond) 2009 33 Suppl 1 S11 5 19363500
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Sensory neurons that detect stretch and nutrients in the digestive system
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Alhadeff, A. L., Rupprecht, L. E., & Hayes, M. R. (2012) · Endocrinology · doi:10.1210/en.2011-1443 · Cited by 515 · see citing works
Self-citationKanoski, S. E., Fortin, S. M., Arnold, M., Grill, H. J., & Hayes, M. R. (2011) · Endocrinology · doi:10.1210/en.2011-0174 · Cited by 347 · see citing works
Self-citationGLP-1 and weight loss: unraveling the diverse neural circuitry
Kanoski, S. E., Hayes, M. R., & Skibicka, K. P. (2016) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00520.2015 · Cited by 290 · see citing works
Self-citationKanoski, S. E., Rupprecht, L. E., Fortin, S. M., De Jonghe, B. C., & Hayes, M. R. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.12.022 · Cited by 273 · see citing works
Self-citationChuong, V., Farokhnia, M., Khom, S., Pince, C. L., Elvig, S. K., Vlkolinsky, R., Marchette, R. C. N., Koob, G. F., Roberto, M., Vendruscolo, L. F., et al. (2023) · JCI Insight · doi:10.1172/jci.insight.170671 · Cited by 214 · see citing works
The central GLP-1: implications for food and drug reward
Skibicka, K. P. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00181 · Cited by 188 · see citing works
Dissociable hindbrain GLP1R circuits for satiety and aversion
Huang, K.-P., Acosta, A. A., Ghidewon, M. Y., McKnight, A. D., Almeida, M. S., Nyema, N. T., Hanchak, N. D., Patel, N., Gbenou, Y. S. K., Adriaenssens, A. E., et al. (2024) · Nature · doi:10.1038/s41586-024-07685-6 · Cited by 166 · see citing works
Richard, J. E., Anderberg, R. H., Göteson, A., Gribble, F. M., Reimann, F., & Skibicka, K. P. (2015) · PLOS ONE · doi:10.1371/journal.pone.0119034 · Cited by 168 · see citing works
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Self-citationAstrocytes Regulate GLP-1 Receptor-Mediated Effects on Energy Balance
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Alcohol-mediated behaviours and the gut-brain axis; with focus on glucagon-like peptide-1
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Study on the comorbid mechanisms of sarcopenia and late-life depression
Wu, J., Tang, J., Huang, D., Wang, Y., Zhou, E., Ru, Q., Xu, G., Chen, L., & Wu, Y. (2025) · Behavioural Brain Research · doi:10.1016/j.bbr.2025.115538 · Cited by 12 · see citing works
- Authors
- Hayes, M. R., De Jonghe, B. C., & Kanoski, S. E.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Hayes, Matthew R.
- Venue
- Physiology & Behavior
- Publisher
- Elsevier BV
- Published
- 2010-07
- Volume
- 100
- Issue
- 5
- Pages
- 503-510
- ISSN
- 0031-9384 (ISSN-L)
- PMC
- PMC2886183
- OpenAlex
- W2058747032
- Cited by
- 173
- References
- 121
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 5 · 2023: 4 · 2022: 7 · 2021: 11 · 2020: 9 · 2019: 8 · 2018: 11 · 2017: 12 · 2016: 12 · 2015: 17 · 2014: 13 · 2013: 16 · 2012: 14
- FWCI
- 1.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Physiology & Behavior (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH-NIDDK (077484)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- GLP-1 receptor, energy balance, obesity, type 2 diabetes, nucleus tractus solitarius, vagal afferents, gut-brain signaling, food intake regulation, incretin effect, GLP-1 receptor signaling
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Animals, Drug Administration Routes, Eating, Energy Metabolism, Humans, Signal Transduction, Receptors, Glucagon, Glucagon-Like Peptide 1, Incretins
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