GLP‐1 Receptor Agonism Exacerbates Activity‐Based Anorexia in Mice
- 1Department of Integrative Physiology and Neuroscience Washington State University Pullman Washington USA
Abstract
Objective: Glucagon‐like peptide‐1 receptor (GLP‐1R) agonists reduce food intake and body weight, suggesting they should be avoided in anorexia nervosa. However, preclinical evidence that these drugs reduce activity and reward‐seeking behavior raises the possibility that they might attenuate the compulsive‐like hyperactivity central to ABA pathology and slow weight loss. Here, we employed a widely used rodent model of AN (activity‐based anorexia, ABA) to determine whether a GLP‐1R agonist would worsen or rather lessen weight loss and hyperactivity.
Method: Female mice that had continuous access to a running wheel and time‐restricted food availability received systemic administration of a GLP‐1R agonist, a GLP‐1R antagonist, or vehicle once daily before food presentation (N = 10/group).
Results: GLP‐1R agonist treatment exacerbated ABA‐associated weight loss, confirming the concern that appetite suppression would worsen outcomes and failing to support the possibility that reduced compulsive‐like activity might provide benefit. This effect was driven by a further suppression of food intake, while wheel running remained unchanged. Pharmacological blockade of GLP‐1R signaling had no detectable effect on any parameter monitored relative to vehicle controls.
Discussion: These findings provide the first experimental evidence that GLP‐1R agonism worsens outcomes in an animal model of anorexia nervosa. The lack of effect of GLP‐1R antagonism suggests endogenous GLP‐1 signaling does not substantially contribute to ABA pathology. Together, these data raise caution regarding the use of GLP‐1R agonists in individuals vulnerable to restrictive eating as they are unlikely to reduce the motivation for excessive activity and can further reduce food intake.
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BibTeX
@article{thakar2026glp1,
title = {{GLP‐1 Receptor Agonism Exacerbates Activity‐Based Anorexia in Mice}},
author = {Amit Thakar and Travis E. Brown and Shane T. Hentges},
journal = {The International Journal of Eating Disorders},
year = {2026},
month = jul,
doi = {10.1002/eat.70169},
url = {https://doi.org/10.1002/eat.70169},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - GLP‐1 Receptor Agonism Exacerbates Activity‐Based Anorexia in Mice
AU - Amit Thakar
AU - Travis E. Brown
AU - Shane T. Hentges
PY - 2026
DA - 2026/07/08
JO - The International Journal of Eating Disorders
DO - 10.1002/eat.70169
UR - https://doi.org/10.1002/eat.70169
AB - Objective: Glucagon‐like peptide‐1 receptor (GLP‐1R) agonists reduce food intake and body weight, suggesting they should be avoided in anorexia nervosa. However, preclinical evidence that these drugs reduce activity and reward‐seeking behavior raises the possibility that they might attenuate the compulsive‐like hyperactivity central to ABA pathology and slow weight loss. Here, we employed a widely used rodent model of AN (activity‐based anorexia, ABA) to determine whether a GLP‐1R agonist would worsen or rather lessen weight loss and hyperactivity. Method: Female mice that had continuous access to a running wheel and time‐restricted food availability received systemic administration of a GLP‐1R agonist, a GLP‐1R antagonist, or vehicle once daily before food presentation (N = 10/group). Results: GLP‐1R agonist treatment exacerbated ABA‐associated weight loss, confirming the concern that appetite suppression would worsen outcomes and failing to support the possibility that reduced compulsive‐like activity might provide benefit. This effect was driven by a further suppression of food intake, while wheel running remained unchanged. Pharmacological blockade of GLP‐1R signaling had no detectable effect on any parameter monitored relative to vehicle controls. Discussion: These findings provide the first experimental evidence that GLP‐1R agonism worsens outcomes in an animal model of anorexia nervosa. The lack of effect of GLP‐1R antagonism suggests endogenous GLP‐1 signaling does not substantially contribute to ABA pathology. Together, these data raise caution regarding the use of GLP‐1R agonists in individuals vulnerable to restrictive eating as they are unlikely to reduce the motivation for excessive activity and can further reduce food intake.
SN - 0276-3478
SN - 1098-108X
ER -