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Research Articles, Systems/Circuits

Glucagon-Like Peptide-1 Receptors in the Gustatory Cortex Influence Food Intake

Amanda M. Dossat, Milayna M. Kokoska, Jessica R. Whitaker-Fornek, Sarah E. Sniffen, Aishwarya S. Kulkarni, Erica S. Levitt and Daniel W. Wesson
Journal of Neuroscience 7 June 2023, 43 (23) 4251-4261; DOI: https://doi.org/10.1523/JNEUROSCI.1668-22.2023
Amanda M. Dossat
Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, Florida 32610
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Milayna M. Kokoska
Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, Florida 32610
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Jessica R. Whitaker-Fornek
Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, Florida 32610
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Sarah E. Sniffen
Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, Florida 32610
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Aishwarya S. Kulkarni
Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, Florida 32610
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Erica S. Levitt
Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, Florida 32610
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Daniel W. Wesson
Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, Florida 32610
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Abstract

The gustatory cortex (GC) region of the insular cortex processes taste information in manners important for taste-guided behaviors, including food intake itself. In addition to oral gustatory stimuli, GC activity is also influenced by physiological states including hunger. The specific cell types and molecular mechanisms that provide the GC with such abilities are unclear. Glucagon-like peptide 1 (GLP-1) is produced by neurons in the brain, where it can act on GLP-1 receptor-expressing (GLP-1R+) neurons found in several brain regions. In these brain regions, GLP-1R agonism suppresses homeostatic food intake and dampens the hedonic value of food. Here, we report in mice of both sexes that cells within the GC express Glp1r mRNA and further, by ex vivo brain slice recordings, that GC GLP-1R+ neurons are depolarized by the selective GLP-1R agonist, exendin-4. Next we found that chemogenetic stimulation of GLP-1R+ neurons, and also pharmacological stimulation of GC-GLP-1Rs themselves, both reduced homeostatic food intake. When mice were chronically maintained on diets with specific fat contents and then later offered foods with new fat contents, we also found that GLP-1R agonism reduced food intake toward foods with differing fat contents, indicating that GC GLP-1R influences may depend on palatability of the food. Together, these results provide evidence for a specific cell population in the GC that may hold roles in both homeostatic and hedonic food intake.

SIGNIFICANCE STATEMENT The present study demonstrates that a population of neurons in the GC region of the insular cortex expresses receptors for GLP-1Rs, these neurons are depolarized by agonism of GLP-1Rs, and GC GLP-1Rs can influence food intake on their activation, including in manners depending on food palatability. This work is significant by adding to our understanding of the brain systems that mediate ingestive behavior, which holds implications for metabolic diseases.

  • feeding
  • gustation
  • ingestive behavior

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The Journal of Neuroscience: 43 (23)
Journal of Neuroscience
Vol. 43, Issue 23
7 Jun 2023
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Glucagon-Like Peptide-1 Receptors in the Gustatory Cortex Influence Food Intake
Amanda M. Dossat, Milayna M. Kokoska, Jessica R. Whitaker-Fornek, Sarah E. Sniffen, Aishwarya S. Kulkarni, Erica S. Levitt, Daniel W. Wesson
Journal of Neuroscience 7 June 2023, 43 (23) 4251-4261; DOI: 10.1523/JNEUROSCI.1668-22.2023

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Glucagon-Like Peptide-1 Receptors in the Gustatory Cortex Influence Food Intake
Amanda M. Dossat, Milayna M. Kokoska, Jessica R. Whitaker-Fornek, Sarah E. Sniffen, Aishwarya S. Kulkarni, Erica S. Levitt, Daniel W. Wesson
Journal of Neuroscience 7 June 2023, 43 (23) 4251-4261; DOI: 10.1523/JNEUROSCI.1668-22.2023
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Keywords

  • feeding
  • gustation
  • ingestive behavior

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