Cited by 79Regulation of Appetite and ObesityNeuropeptides and Animal PhysiologyDiabetes Treatment and Management

Brain activation following peripheral administration of the GLP-1 receptor agonist exendin-4

Baraboi, Elena-Dana, St-Pierre, David H., Shooner, Julie, Timofeeva, Elena, Richard, Denis·2011·American Journal of Physiology-Regulatory, Integrative and Comparative Physiology

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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Crossref · 10.1152/ajpregu.00424.2010

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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.

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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
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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