Hypothalamic POMC Neurons Gate the Fear-Feeding Trade-Off.
- 1University of Bordeaux, INSERM, Neurocentre Magendie, U1215, Bordeaux, France.
Abstract
To survive, animals must constantly balance the need to obtain food with the need to avoid danger. Feeding is essential, yet perceived danger shifts priority toward safety and transiently suppresses food intake, even when organisms are hungry. Hypothalamic pro-opiomelanocortin (POMC) neurons align metabolic outputs with energy demands and control feeding. However, the role of POMC neurons in determining the trade-off between feeding and threat responses remains unclear. Here, fasted mice are exposed to a fear-conditioning paradigm to examine how POMC neurons influence the choice between feeding and defensive behaviors. Behavioral analyses combined with chemogenetic, neuroanatomical, and molecular approaches show that activation of POMC neurons suppresses feeding during a learned threat and it is associated with corticotropin releasing hormone (CRH) neuron-dependent activation of the hypothalamic-pituitary-adrenal (HPA) axis. These effects require cannabinoid type 1 receptor (CB1R) signaling in POMC neurons, uncovering a POMC-CB1R pathway that tunes behavioral flexibility under a perceived threat. Collectively, the data identify POMC neurons as key integrators of metabolic and stress signals that bias decision making between feeding and threat-avoidance behaviors.
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BibTeX
@article{miralpeix2026hypothalamic,
title = {{Hypothalamic POMC Neurons Gate the Fear-Feeding Trade-Off.}},
author = {Cristina Miralpeix and Abel Eraso-Pichot and Vincent Simon and Victor Jouque and Melissa Sadallah and Samantha Clark and Philippe Zizzari and Urszula Skupio and Ana Covelo and Nathalie Dupuy and Jean Charles Nicolas and Astrid Cannich and Thierry Leste-Lasserre and Guillaume Laplagne and Carmelo Quarta and Giovanni Marsicano and Daniela Cota},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
year = {2026},
month = oct,
doi = {10.1002/advs.78379},
url = {https://europepmc.org/article/MED/42902516},
note = {CC BY},
}
RIS
TY - JOUR
TI - Hypothalamic POMC Neurons Gate the Fear-Feeding Trade-Off.
AU - Cristina Miralpeix
AU - Abel Eraso-Pichot
AU - Vincent Simon
AU - Victor Jouque
AU - Melissa Sadallah
AU - Samantha Clark
AU - Philippe Zizzari
AU - Urszula Skupio
AU - Ana Covelo
AU - Nathalie Dupuy
AU - Jean Charles Nicolas
AU - Astrid Cannich
AU - Thierry Leste-Lasserre
AU - Guillaume Laplagne
AU - Carmelo Quarta
AU - Giovanni Marsicano
AU - Daniela Cota
PY - 2026
DA - 2026/10/20
JO - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
DO - 10.1002/advs.78379
UR - https://europepmc.org/article/MED/42902516
AB - To survive, animals must constantly balance the need to obtain food with the need to avoid danger. Feeding is essential, yet perceived danger shifts priority toward safety and transiently suppresses food intake, even when organisms are hungry. Hypothalamic pro-opiomelanocortin (POMC) neurons align metabolic outputs with energy demands and control feeding. However, the role of POMC neurons in determining the trade-off between feeding and threat responses remains unclear. Here, fasted mice are exposed to a fear-conditioning paradigm to examine how POMC neurons influence the choice between feeding and defensive behaviors. Behavioral analyses combined with chemogenetic, neuroanatomical, and molecular approaches show that activation of POMC neurons suppresses feeding during a learned threat and it is associated with corticotropin releasing hormone (CRH) neuron-dependent activation of the hypothalamic-pituitary-adrenal (HPA) axis. These effects require cannabinoid type 1 receptor (CB1R) signaling in POMC neurons, uncovering a POMC-CB1R pathway that tunes behavioral flexibility under a perceived threat. Collectively, the data identify POMC neurons as key integrators of metabolic and stress signals that bias decision making between feeding and threat-avoidance behaviors.
SN - 2198-3844
ER -