POMC AMPKα1 deletion drives male-specific BAT thermogenesis and obesity resistance
7 affiliations
- 1Department of Physiology, CiMUS, University of Santiago de Compostela
- 2CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN)
- 3CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII)
- 4Department of Morphological Sciences, CiMUS, University of Santiago de Compostela
- 5University of Bordeaux, INSERM, Neurocentre Magendie, U1215
- 6Centro Nacional de Investigaciones Cardiovasculares (CNIC)
- 7Service of Ophthalmology, Complejo Hospitalario Universitario de Santiago de Compostela and CiMUS, University of Santiago de Compostela
Abstract
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.
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BibTeX
@article{freireagulleiro2026pomc,
title = {{POMC AMPKα1 deletion drives male-specific BAT thermogenesis and obesity resistance}},
author = {Óscar Freire-Agulleiro and Marcos Rios Garcia and Vitor Ferreira and Patricia Seoane-Collazo and Juan Roa and Ánxela Estévez-Salguero and Alicia Otero-Rey and Jordi Capellades and Francisco Ruiz-Pino and Pablo Garrido-Gil and Vincent Simon and Jean-Charles Nicolas and Juan A López and Cristina Contreras and Laura Liñares-Pose and Francisco Gonzalez and José L Labandeira-García and Jesús Vázquez and Carlos Diéguez and Rubén Nogueiras and Daniela Cota and Oscar Yanes and Guadalupe Sabio and Manuel Tena-Sempere and Carmelo Quarta and Ismael González-García and Miguel López},
journal = {EMBO Reports},
year = {2026},
month = sep,
doi = {10.1038/s44319-026-00915-0},
url = {https://doi.org/10.1038/s44319-026-00915-0},
note = {CC BY},
}
RIS
TY - JOUR
TI - POMC AMPKα1 deletion drives male-specific BAT thermogenesis and obesity resistance
AU - Óscar Freire-Agulleiro
AU - Marcos Rios Garcia
AU - Vitor Ferreira
AU - Patricia Seoane-Collazo
AU - Juan Roa
AU - Ánxela Estévez-Salguero
AU - Alicia Otero-Rey
AU - Jordi Capellades
AU - Francisco Ruiz-Pino
AU - Pablo Garrido-Gil
AU - Vincent Simon
AU - Jean-Charles Nicolas
AU - Juan A López
AU - Cristina Contreras
AU - Laura Liñares-Pose
AU - Francisco Gonzalez
AU - José L Labandeira-García
AU - Jesús Vázquez
AU - Carlos Diéguez
AU - Rubén Nogueiras
AU - Daniela Cota
AU - Oscar Yanes
AU - Guadalupe Sabio
AU - Manuel Tena-Sempere
AU - Carmelo Quarta
AU - Ismael González-García
AU - Miguel López
PY - 2026
DA - 2026/09/01
JO - EMBO Reports
DO - 10.1038/s44319-026-00915-0
UR - https://doi.org/10.1038/s44319-026-00915-0
AB - 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.
SN - 1469-3178
ER -