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
- PMID: 22128031
- PMCID: PMC3275387
- DOI: 10.1210/en.2011-1443
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
Abstract
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.
Figures
![Fig. 1.](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3275387/bin/zee0021262720001.gif)
![Fig. 2.](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3275387/bin/zee0021262720002.gif)
![Fig. 3.](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3275387/bin/zee0021262720003.gif)
![Fig. 4.](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3275387/bin/zee0021262720004.gif)
![Fig. 5.](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3275387/bin/zee0021262720005.gif)
![Fig. 6.](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3275387/bin/zee0021262720006.gif)
Similar articles
-
Glucagon-Like Peptide-1 Receptor Signaling in the Lateral Dorsal Tegmental Nucleus Regulates Energy Balance.Neuropsychopharmacology. 2018 Feb;43(3):627-637. doi: 10.1038/npp.2017.225. Epub 2017 Sep 18. Neuropsychopharmacology. 2018. PMID: 28920591 Free PMC article.
-
Glucagon-like peptide-1 receptor activation in the nucleus accumbens core suppresses feeding by increasing glutamatergic AMPA/kainate signaling.J Neurosci. 2014 May 14;34(20):6985-92. doi: 10.1523/JNEUROSCI.0115-14.2014. J Neurosci. 2014. PMID: 24828651 Free PMC article.
-
Hindbrain nucleus tractus solitarius glucagon-like peptide-1 receptor signaling reduces appetitive and motivational aspects of feeding.Am J Physiol Regul Integr Comp Physiol. 2014 Aug 15;307(4):R465-70. doi: 10.1152/ajpregu.00179.2014. Epub 2014 Jun 18. Am J Physiol Regul Integr Comp Physiol. 2014. PMID: 24944243 Free PMC article.
-
GLP-1 and weight loss: unraveling the diverse neural circuitry.Am J Physiol Regul Integr Comp Physiol. 2016 May 15;310(10):R885-95. doi: 10.1152/ajpregu.00520.2015. Epub 2016 Mar 30. Am J Physiol Regul Integr Comp Physiol. 2016. PMID: 27030669 Free PMC article. Review.
-
Glucagon-like peptide 1 interacts with ghrelin and leptin to regulate glucose metabolism and food intake through vagal afferent neuron signaling.J Nutr. 2015 Apr;145(4):672-80. doi: 10.3945/jn.114.206029. Epub 2015 Feb 4. J Nutr. 2015. PMID: 25833771 Free PMC article. Review.
Cited by
-
Associations of semaglutide with incidence and recurrence of alcohol use disorder in real-world population.Nat Commun. 2024 May 28;15(1):4548. doi: 10.1038/s41467-024-48780-6. Nat Commun. 2024. PMID: 38806481 Free PMC article.
-
Metformin and the Liver: Unlocking the Full Therapeutic Potential.Metabolites. 2024 Mar 25;14(4):186. doi: 10.3390/metabo14040186. Metabolites. 2024. PMID: 38668314 Free PMC article. Review.
-
Synthetic exendin-4 disrupts responding to reward predictive incentive cues in male rats.Front Behav Neurosci. 2024 Mar 14;18:1363497. doi: 10.3389/fnbeh.2024.1363497. eCollection 2024. Front Behav Neurosci. 2024. PMID: 38549620 Free PMC article.
-
Acute and Chronic Exposure to Linagliptin, a Selective Inhibitor of Dipeptidyl Peptidase-4 (DPP-4), Has an Effect on Dopamine, Serotonin and Noradrenaline Level in the Striatum and Hippocampus of Rats.Int J Mol Sci. 2024 Mar 5;25(5):3008. doi: 10.3390/ijms25053008. Int J Mol Sci. 2024. PMID: 38474255 Free PMC article.
-
Dopamine neuron activity evoked by sucrose and sucrose-predictive cues is augmented by peripheral and central manipulations of glucose availability.Eur J Neurosci. 2024 May;59(10):2419-2435. doi: 10.1111/ejn.16214. Epub 2023 Dec 6. Eur J Neurosci. 2024. PMID: 38057909
References
-
- Baggio LL, Drucker DJ. 2007. Biology of incretins: GLP-1 and GIP. Gastroenterology 132:2131–2157 - PubMed
-
- Lovshin JA, Drucker DJ. 2009. Incretin-based therapies for type 2 diabetes mellitus. Nat Rev Endocrinol 5:262–269 - PubMed
-
- Holst JJ. 2007. The physiology of glucagon-like peptide 1. Physiol Rev 87:1409–1439 - PubMed
-
- Knudsen LB. 2010. Liraglutide: the therapeutic promise from animal models. Int J Clin Pract Suppl 167:4–11 - PubMed