Vagal afferents mediate early satiation and prevent flavour avoidance learning in response to intraperitoneally infused exendin-4
- PMID: 22827554
- DOI: 10.1111/j.1365-2826.2012.02364.x
Vagal afferents mediate early satiation and prevent flavour avoidance learning in response to intraperitoneally infused exendin-4
Abstract
Glucagon-like peptide-1 receptor (GLP-1R) agonists such as exendin-4 (Ex-4) affect eating and metabolism and are potential candidates for treating obesity and type II diabetes. In the present study, we tested whether vagal afferents mediate the eating-inhibitory and avoidance-inducing effects of Ex-4. Subdiaphragmatic vagal deafferentation (SDA) blunted the short-term (< 1 h) but not long-term eating-inhibitory effect of i.p.-infused Ex-4 (0.1 μg/kg) in rats. A dose of 1 μg/kg Ex-4 reduced 0.5, 1, 2 and 4 h cumulative food intake in SDA and sham-operated rats to a similar extent. Paradoxically, SDA but not sham rats developed a conditioned flavour avoidance (CFA) after i.p. Ex-4 (0.1 μg/kg). SDA completely blunted the induction of c-Fos expression by Ex-4 in the hypothalamic paraventricular nucleus. Ex-4, however, increased the number of c-Fos expressing cells, independent of intact vagal afferents, in the nucleus accumbens and in the central nucleus of the amygdala, the lateral external parabrachial nucleus, the caudal ventrolateral medulla and the dorsal vagal complex. These data suggest that intact vagal afferents are only necessary for the full expression of the early satiating effect of Ex-4 but not for later eating-inhibitory actions, when circulating Ex-4 might reach the brain via the circulation. Our data also dissociate the satiating and avoidance-inducing effects of the low Ex-4 dose tested under our conditions and suggest that vagal afferent signalling may protect against the development of CFA. Taken together, these findings reveal a complex role of vagal afferents in mediating the effects of GLP-1R activation on ingestive behaviour.
© 2012 The Authors. Journal of Neuroendocrinology © 2012 British Society for Neuroendocrinology.
Similar articles
-
Gut vagal afferents are not necessary for the eating-stimulatory effect of intraperitoneally injected ghrelin in the rat.J Neurosci. 2006 Oct 25;26(43):11052-60. doi: 10.1523/JNEUROSCI.2606-06.2006. J Neurosci. 2006. PMID: 17065447 Free PMC article.
-
The common hepatic branch of the vagus is not required to mediate the glycemic and food intake suppressive effects of glucagon-like-peptide-1.Am J Physiol Regul Integr Comp Physiol. 2011 Nov;301(5):R1479-85. doi: 10.1152/ajpregu.00356.2011. Epub 2011 Aug 17. Am J Physiol Regul Integr Comp Physiol. 2011. PMID: 21849636 Free PMC article.
-
Peripheral and central GLP-1 receptor populations mediate the anorectic effects of peripherally administered GLP-1 receptor agonists, liraglutide and exendin-4.Endocrinology. 2011 Aug;152(8):3103-12. doi: 10.1210/en.2011-0174. Epub 2011 Jun 21. Endocrinology. 2011. PMID: 21693680 Free PMC article.
-
Peripheral glucagon-like peptide-1 (GLP-1) and satiation.Physiol Behav. 2011 Nov 30;105(1):71-6. doi: 10.1016/j.physbeh.2011.02.038. Epub 2011 Mar 1. Physiol Behav. 2011. PMID: 21371486 Review.
-
Intestinal glucagon-like peptide-1 effects on food intake: Physiological relevance and emerging mechanisms.Peptides. 2020 Sep;131:170342. doi: 10.1016/j.peptides.2020.170342. Epub 2020 Jun 6. Peptides. 2020. PMID: 32522585 Review.
Cited by
-
A review of an investigational drug retatrutide, a novel triple agonist agent for the treatment of obesity.Eur J Clin Pharmacol. 2024 May;80(5):669-676. doi: 10.1007/s00228-024-03646-0. Epub 2024 Feb 17. Eur J Clin Pharmacol. 2024. PMID: 38367045 Review.
-
Gastric vagal afferent signaling to the basolateral amygdala mediates anxiety-like behaviors in experimental colitis mice.JCI Insight. 2023 Jun 22;8(12):e161874. doi: 10.1172/jci.insight.161874. JCI Insight. 2023. PMID: 37200091 Free PMC article.
-
Microbiota-gut-brain axis: relationships among the vagus nerve, gut microbiota, obesity, and diabetes.Acta Diabetol. 2023 Aug;60(8):1007-1017. doi: 10.1007/s00592-023-02088-x. Epub 2023 Apr 14. Acta Diabetol. 2023. PMID: 37058160 Free PMC article. Review.
-
The Relationship Between the Blood-Brain-Barrier and the Central Effects of Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter-2 Inhibitors.Diabetes Metab Syndr Obes. 2022 Aug 22;15:2583-2597. doi: 10.2147/DMSO.S375559. eCollection 2022. Diabetes Metab Syndr Obes. 2022. PMID: 36035518 Free PMC article. Review.
-
Glucagon-like peptide-1 (GLP-1) signalling in the brain: From neural circuits and metabolism to therapeutics.Br J Pharmacol. 2022 Feb;179(4):600-624. doi: 10.1111/bph.15682. Epub 2021 Nov 4. Br J Pharmacol. 2022. PMID: 34519026 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources