| First Author | Phair IR | Year | 2023 |
| Journal | Mol Metab | Volume | 68 |
| Pages | 101661 | PubMed ID | 36586434 |
| Mgi Jnum | J:339509 | Mgi Id | MGI:7427966 |
| Doi | 10.1016/j.molmet.2022.101661 | Citation | Phair IR, et al. (2022) AMPK integrates metabolite and kinase-based immunometabolic control in macrophages. Mol Metab 68:101661 |
| abstractText | 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 AMPKalpha1. RESULTS: Comparing macrophages with AMPKalpha1 catalytic subunit deletion with wild-type, inflammatory markers are largely unchanged in unstimulated cells, but with an LPS stimulus, AMPKalpha1 knockout leads to a striking M1 hyperpolarisation. Deletion of AMPKalpha1 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 AMPKalpha1 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. |
