Year: 2026
Type: article
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.
Source: Advanced Science
DOI: 10.1002/advs.78379
Authors: Cristina Miralpeix, Abel Eraso‐Pichot, Vincent Simon, Victor Jouque, Melissa Sadallah, Samantha Clark, Philippe Zizzari, Urszula Skupio, Ana Covelo, Nathalie Dupuy, Jean Charles Nicolas, Astrid Cannich, Thierry Leste‐Lasserre, Guillaume Laplagne, Carmelo Quarta, Giovanni Marsicano, Daniela Cota
Institutions: Université de Bordeaux, Inserm, Neurocentre Magendie
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,730
Awards: Role of Tbx3 in directing the functional identity of POMC neurons in obesity, Uncovering the neuro-immune mechanisms driving the memory of obesity, Role of the POMC-ventral striatal neurocircuit in the development of diet-induced obesity, G5296751580, Glucose homeostasis alteration implicates a novel hypothalamic inflammatory pathway., G5959744682, G6069939831, University of Bordeaux Neurocampus Graduate School, G7080048889, Unmasking Mechanisms of Neuroendocrine Fate Reprogramming in Response to Maternal Obesity, Role of mitochondrial cannabinoid type 1 receptor in hypothalamic circuits and its interaction with mTORC1 pathway during obesity., G7878646764, G996255883
OpenAlex ID: W7223140887