Tabitha Johnson
Pronouns: she/her
Research Mentor(s): David Olson
Research Mentor School/College/Department: Pediatrics / Medicine
Program:
Authors: Tabitha Johnson, Gizem Kurt, David Olson
Session: Session 2: 10:00 am – 10:50 am
Poster: 33
Abstract
The effect of Glp1R rescue in GPR10-expressing neurons on feeding and body weight regulation. Obesity is a risk factor in developing serious health conditions, but treatment options are limited. One current treatment is Glucagon-like peptide 1 receptor(Glp1R) agonists (e.g.liraglutide). However, adverse effects from agonists targeting whole body Glp1Rs makes it harder for patients to follow treatment. The area postrema(AP) has the highest percentage of liraglutide-activated neurons in the hindbrain, suggesting that this region is critical for Glp1R agonist actions. However, AP Glp1R neurons are heterogenous. Identifying which subpopulation of AP Glp1R neurons might be responsible for the anorexic actions of Glp1R agonists may help us develop targeted therapies. By use of recombinase technology, our lab is doing genetic re-activation studies to assess AP Glp1R subpopulations. One of the subpopulations, G-protein coupled receptor 10(GPR10) expressing neurons, are implicated in body weight regulation. Therefore, we hypothesized that the specific re-activation of Glp1R in GPR10 neurons rescues the liraglutide-induced anorexia. To test this hypothesis, we used genetically modified mice that are either expressing Glp1R, lacking Glp1R, or expressing Glp1R only in GPR10 neurons. To determine whether rescuing Glp1R expression in GPR10 neurons is sufficient to restore liraglutide-induced activation in the AP, we applied cFos immunostaining and microscopy on brain samples from liraglutide or saline injected mice. We found that rescuing Glp1R expression in GPR10 neurons partially restores normal activation patterns in the AP. This data partially supports our hypothesis. In the future, we will study the feeding behavior of these groups to observe the effects of the Glp1R reactivation in GPR10 neurons. In conclusion, we found that rescuing Glp1R expression in GPR10 neurons partially restores the response to liraglutide in the AP and further studies are needed to determine behavioral effects of this rescue. If there is a potential obesity treatment found without adverse effects, it would ease the ability to follow treatment and more patients would be successful.
