Dataset Information
AMPK integrates metabolite and kinase-based immunometabolic control in macrophages.
Ontology highlight
ABSTRACT: Objective
Previous mechanistic studies on immunometabolism have focused on metabolite-based paradigms of regulation, such as itaconate. Here, we, demonstrate integration of metabolite and kinase-based immunometabolic control by AMP kinase.Methods
We combined whole cell quantitative proteomics with gene knockout of AMPKα1.Results
Comparing macrophages with AMPKα1 catalytic subunit deletion with wild-type, inflammatory markers are largely unchanged in unstimulated cells, but with an LPS stimulus, AMPKα1 knockout leads to a striking M1 hyperpolarisation. Deletion of AMPKα1 also resulted in increased expression of rate-limiting enzymes involved in itaconate synthesis, metabolism of glucose, arginine, prostaglandins and cholesterol. Consistent with this, we observed functional changes in prostaglandin synthesis and arginine metabolism. Selective AMPKα1 activation also unlocks additional regulation of IL-6 and IL-12 in M1 macrophages.Conclusions
Together, our results validate AMPK as a pivotal immunometabolic regulator in macrophages.
SUBMITTER: Phair IR
PROVIDER: S-EPMC9842865 | biostudies-literature | 2023 Feb
REPOSITORIES: biostudies-literature
Publications
AMPK integrates metabolite and kinase-based immunometabolic control in macrophages.
Molecular metabolism 20221228
<h4>Objective</h4>Previous mechanistic studies on immunometabolism have focused on metabolite-based paradigms of regulation, such as itaconate. Here, we, demonstrate integration of metabolite and kinase-based immunometabolic control by AMP kinase.<h4>Methods</h4>We combined whole cell quantitative proteomics with gene knockout of AMPKα1.<h4>Results</h4>Comparing macrophages with AMPKα1 catalytic subunit deletion with wild-type, inflammatory markers are largely unchanged in unstimulated cells, bu ...[more]