2026-09-20T17:26:20Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/277172026-09-16T00:15:32Zcom_20.500.12105_2327com_20.500.12105_2290col_20.500.12105_16991

00925njm 22002777a 4500 dc Freire-Agulleiro, Óscar author Rios Garcia, Marcos author Ferreira, Vitor author Seoane-Collazo, Patricia author Roa, Juan author Estévez-Salguero, Ánxela author Otero-Rey, Alicia author Capellades, Jordi author Ruiz-Pino, Francisco author Garrido-Gil, Pablo author Simon, Vincent author Nicolas, Jean-Charles author López, Juan A author Contreras, Cristina author Liñares-Pose, Laura author Gonzalez, Francisco author Labandeira-García, José L author Vázquez, Jesús author Diéguez, Carlos author Nogueiras, Rubén author Cota, Daniela author Yanes, Oscar author Sabio, Guadalupe author Tena-Sempere, Manuel author Quarta, Carmelo author González-García, Ismael author López, Miguel author 2026-09-01 Proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARC) play a critical role in energy homeostasis. 5'-adenosine monophosphate-activated protein kinase (AMPK) is a serine/threonine kinase, which acts as the main energy sensor in the cell. The heterotrimeric AMPK results from the combination of a catalytic α subunit (α1, α2) with two regulatory subunits, β (β1, β2) and γ (γ1, γ2 and γ3). Hypothalamic AMPK plays a key role in the control of energy balance, but current evidence shows that the precise combination of its heterotrimeric components determines its physiological action. Our findings show that AMPKα1 ablation in POMC neurons has a sex-dependent protective effect against diet-induced obesity because of increased thermogenesis in brown adipose tissue (BAT) in males, but not in females. At the molecular level, deletion of AMPKα1 in POMC neurons disrupts the ARC phosphoproteome and is associated with ameliorated endoplasmic reticulum (ER) stress and reduced ceramide content. These findings highlight the complex function of the different AMPK subunits in the hypothalamic regulation of energy balance. EMBO Rep. 2026 Sep 1. EMBO REPORTS 42680850 https://hdl.handle.net/20.500.12105/27717 POMC AMPKα1 deletion drives male-specific BAT thermogenesis and obesity resistance.