Glucagon-like peptide-1 receptors in the gustatory cortex influence food intake.

The gustatory region of the insular cortex (GC) 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 afford the GC with such abilities are unclear. Glucagon-like peptide 1 (GLP-1) is produced by neurons in the brain whereafter it can act upon GLP-1 receptor-expressing (GLP-1R+) neurons found in several brain regions. In these brain regions, GLP-1 receptor (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 (Ex-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 towards foods with differing fat contents - indicating that GC GLP-1R influences may depend upon palatability of the food. Together, these results provide evidence for a specific cell population in the GC which may hold roles in both homeostatic and hedonic food intake. SIGNIFICANCE STATEMENT: The present study demonstrates that a population of neurons in the gustatory cortex (GC) region of the insular cortex express receptors for glucagon-like peptide 1 (GLP-1Rs), these neurons are depolarized by agonism of GLP-1Rs, and that GC GLP-1Rs can influence food intake upon their activation, including in manners depending upon 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.