Brain activation following peripheral administration of the GLP-1 receptor agonist exendin-4
Abstract
The aim of our study was to investigate the anorectic and brain stimulatory effects of various doses of exendin-4 (Ex-4) and to investigate the role of the vagus nerve in Ex-4-induced brain activation. A dose-related increase in c- fos mRNA expression was observed following Ex-4 administration (0.155–15.5 μg/kg). Doses of Ex-4 that caused anorexia without aversive effects (0.155, 0.775 μg/kg) induced c- fos expression in the hypothalamic arcuate and paraventricular (PVH; parvocellular) nuclei as well as in the limbic and brainstem structures. Doses of Ex-4 that caused aversion (1.55, 15.5 μg/kg) stimulated the same regions (in a more intense way) and additionally activated the magnocellular hypothalamic structures (supraoptic nucleus and PVH magnocellular). The brain c- fos pattern induced by Ex-4 showed both similarities and differences with that induced by refeeding. Subdiaphragmatic vagotomy significantly blunted the stimulation of c- fos mRNA expression induced by Ex-4 in the nodose ganglion, the medial part of nucleus of the solitary tract, and the parvocellular division of the PVH. Pretreatment with Ex-9-39 (330 μg/kg ip) impaired the neuronal activation evoked by Ex-4 in all brain regions and in the nodose ganglion. Effects of Ex-4 on hypothalamic-pituitary-adrenal axis activity were not altered by vagotomy. Results of this study demonstrate and relate the anorectic and brain stimulatory effects of aversive and nonaversive doses of Ex-4 and indicate that the activation of specific central regions induced by the peripheral administration of Ex-4 is, at least in part, dependent on the integrity of the vagus nerve.
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Semaglutide's gastrointestinal side effects might arise from altered gastric emptying, intestinal motility, secretion of other gut peptide hormones, or direct or indirect central nervous system actions.
“They could be the result of the effect of the medication on gastrointestinal functions such as gastric emptying, intestinal motility, secondary changes in the secretion of other gastrointestinal peptide hormones, and/or direct or indirect effects on the central nervous system.(51)”
From Semaglutide for the treatment of obesity (2023) · cites this paper as [51]
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- Authors
- Baraboi, E.-D., St-Pierre, D. H., Shooner, J., Timofeeva, E., & Richard, D.
- Affiliations
- Canadian Institutes of Health Research (CA)
- Corresponding author
- Richard, Denis
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 2011-10
- Volume
- 301
- Issue
- 4
- Pages
- R1011-R1024
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- OpenAlex
- W2124762650
- Cited by
- 79
- References
- 61
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 5 · 2023: 3 · 2022: 2 · 2021: 6 · 2020: 8 · 2019: 3 · 2018: 5 · 2017: 2 · 2016: 5 · 2015: 7 · 2014: 9 · 2013: 10 · 2012: 6
- FWCI
- 3.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- exendin-4, GLP-1 receptor agonists, Fos expression, vagus nerve, vagotomy, nodose ganglion, paraventricular nucleus, hypothalamus, anorexia, aversive effects, hypothalamic-pituitary-adrenal axis, refeeding, appetite regulation
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Exenatide, Animals, Brain, Corticotropin-Releasing Hormone, Dose-Response Relationship, Drug, Hypothalamo-Hypophyseal System, Hypothalamus, Male, Nodose Ganglion, Paraventricular Hypothalamic Nucleus, Peptides, Pituitary-Adrenal System, Vagus Nerve, Venoms, Proto-Oncogene Proteins c-fos, Rats, Wistar, Receptors, Glucagon, Models, Animal, Rats
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