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Peer-reviewedCC BY-NC-ND 4.0Molecular Metabolism

Parabrachial CGRP neurons mediate incretin-induced aversion and anti-aversion, but not anorexia or weight loss

  • Haley S. Province1,2,3
  • Nathan A. Leong4
  • Nicholas J. Conley1
  • Nikolas W. Hayes1,2
  • Esther Tang1
  • Lisa R. Beutler1
4 affiliations
  1. 1Department of Medicine, Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University, Chicago, IL 60611, USA
  2. 2Northwestern Interdepartmental Neuroscience Graduate Program, Northwestern University, Chicago, IL 60611, USA
  3. 3Medical Scientist Training Program, Northwestern University, Chicago, IL 60611, USA
  4. 4Department of Neurobiology, Northwestern University, Evanston, IL 60208, USA
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Abstract

Incretin mimetics such as the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide cause decreased food intake, weight loss, and aversion. Here, we examined the extent to which parabrachial calcitonin gene-related peptide (CGRP) neurons contribute to these effects. Further, we assessed whether glucose-dependent insulinotropic polypeptide receptor (GIPR) agonism alters liraglutide-induced behavior and CGRP neuron activity. We found that liraglutide activates parabrachial CGRP neurons and that this is required for liraglutide-induced aversion, but not anorexia or weight loss. Additionally, treatment with a GIPR agonist (GIPRA) or the well-established anti-emetic drug ondansetron ameliorated liraglutide-induced conditioned taste avoidance (CTA) and CGRP neuron activation without affecting acute liraglutide-induced feeding suppression. Taken together, our findings demonstrate that the aversive and anorexigenic effects of liraglutide are mediated by distinct neural mechanisms that can be separably manipulated. Our findings also highlight GIPR agonism as an emerging anti-aversive approach to GLP-1RA-induced malaise while maintaining the beneficial metabolic effects.

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Cite

BibTeXRIS
BibTeX
@article{province2026parabrachial,
  title = {{Parabrachial CGRP neurons mediate incretin-induced aversion and anti-aversion, but not anorexia or weight loss}},
  author = {Haley S. Province and Nathan A. Leong and Nicholas J. Conley and Nikolas W. Hayes and Esther Tang and Lisa R. Beutler},
  journal = {Molecular Metabolism},
  year = {2026},
  month = oct,
  doi = {10.1016/j.molmet.2026.102453},
  url = {https://doi.org/10.1016/j.molmet.2026.102453},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Parabrachial CGRP neurons mediate incretin-induced aversion and anti-aversion, but not anorexia or weight loss
AU  - Haley S. Province
AU  - Nathan A. Leong
AU  - Nicholas J. Conley
AU  - Nikolas W. Hayes
AU  - Esther Tang
AU  - Lisa R. Beutler
PY  - 2026
DA  - 2026/10/06
JO  - Molecular Metabolism
DO  - 10.1016/j.molmet.2026.102453
UR  - https://doi.org/10.1016/j.molmet.2026.102453
AB  - Incretin mimetics such as the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide cause decreased food intake, weight loss, and aversion. Here, we examined the extent to which parabrachial calcitonin gene-related peptide (CGRP) neurons contribute to these effects. Further, we assessed whether glucose-dependent insulinotropic polypeptide receptor (GIPR) agonism alters liraglutide-induced behavior and CGRP neuron activity. We found that liraglutide activates parabrachial CGRP neurons and that this is required for liraglutide-induced aversion, but not anorexia or weight loss. Additionally, treatment with a GIPR agonist (GIPRA) or the well-established anti-emetic drug ondansetron ameliorated liraglutide-induced conditioned taste avoidance (CTA) and CGRP neuron activation without affecting acute liraglutide-induced feeding suppression. Taken together, our findings demonstrate that the aversive and anorexigenic effects of liraglutide are mediated by distinct neural mechanisms that can be separably manipulated. Our findings also highlight GIPR agonism as an emerging anti-aversive approach to GLP-1RA-induced malaise while maintaining the beneficial metabolic effects.
SN  - 2212-8778
ER  -