POMC neuron AMPKα1 ablation attenuates obesity via BAT activation

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 a 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. This makes necessary the study of the role of the different subunits in a cell-specific manner. Our findings show that AMPKα1 ablation in POMC neurons has a protective effect over diet-induced obesity because of increased thermogenesis in brown adipose tissue (BAT). At the molecular level, deletion of AMPKα1 in POMC neurons disrupts the ARC phosphoproteome and is associated with an ameliorated endoplasmic reticulum (ER) stress. These findings highlight the complex function of the different AMPK subunits in the hypothalamic regulation of energy balance.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain, Ventromedial Hypothalamic Nucleus

SUBMITTER: Juan A Lopez  

LAB HEAD: Juan A Lopez

PROVIDER: PXD068034 | Pride | 2026-06-30

REPOSITORIES: Pride