Orexin and pupillary modulation for hunger control
- 1ETH Zürich, Department of Health Sciences and Technology, Neuroscience Center Zürich, Institute for Neuroscience, Schwerzenbach 8603, Switzerland
Abstract
Fasting-based interventions improve metabolic health and are also explored as adjuncts in other clinical settings, but hunger remains a barrier to adherence. Fasting activates AgRP/NPY neurons (ANs), a hunger-promoting population whose inhibition reduces eating in hungry animals. Here we identify hypocretin/orexin neurons (HONs), classically associated with arousal, as rapid suppressors of AN activity. HON ablation increased AN population activity, whereas HON optostimulation rapidly suppressed it. Combined recordings of AN activity and pupil size—a direct arousal metric not previously linked to AN dynamics—revealed that HONs contributed to pupil dilation-associated AN suppression. In fasted mice, sensory stimulation rapidly recruited this pupil-HON pathway, and suppressed AN activity and eating. These findings reveal an arousal–hunger pathway through which self-initiated pupil dilations, or dilations driven by salient environmental events, interrupt fasting-induced hunger signals. They also suggest a framework for noninvasive, sensory-, and pupillometry-guided approaches to hunger control during fasting.
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BibTeX
@article{kosar2026orexin,
title = {{Orexin and pupillary modulation for hunger control}},
author = {Seher Kosar and Eva Bracey and Nikola Grujic and Yihui Du and Daria Peleg-Raibstein and Denis Burdakov},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2026},
month = oct,
doi = {10.1073/pnas.2619759123},
url = {https://doi.org/10.1073/pnas.2619759123},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Orexin and pupillary modulation for hunger control
AU - Seher Kosar
AU - Eva Bracey
AU - Nikola Grujic
AU - Yihui Du
AU - Daria Peleg-Raibstein
AU - Denis Burdakov
PY - 2026
DA - 2026/10/28
JO - Proceedings of the National Academy of Sciences of the United States of America
DO - 10.1073/pnas.2619759123
UR - https://doi.org/10.1073/pnas.2619759123
AB - Fasting-based interventions improve metabolic health and are also explored as adjuncts in other clinical settings, but hunger remains a barrier to adherence. Fasting activates AgRP/NPY neurons (ANs), a hunger-promoting population whose inhibition reduces eating in hungry animals. Here we identify hypocretin/orexin neurons (HONs), classically associated with arousal, as rapid suppressors of AN activity. HON ablation increased AN population activity, whereas HON optostimulation rapidly suppressed it. Combined recordings of AN activity and pupil size—a direct arousal metric not previously linked to AN dynamics—revealed that HONs contributed to pupil dilation-associated AN suppression. In fasted mice, sensory stimulation rapidly recruited this pupil-HON pathway, and suppressed AN activity and eating. These findings reveal an arousal–hunger pathway through which self-initiated pupil dilations, or dilations driven by salient environmental events, interrupt fasting-induced hunger signals. They also suggest a framework for noninvasive, sensory-, and pupillometry-guided approaches to hunger control during fasting.
SN - 0027-8424
SN - 1091-6490
ER -