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Metabolism of inflammation limited by AMPK and pseudo-starvation

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Abstract

Metabolic changes in cells that participate in inflammation, such as activated macrophages and T-helper 17 cells, include a shift towards enhanced glucose uptake, glycolysis and increased activity of the pentose phosphate pathway. Opposing roles in these changes for hypoxia-inducible factor 1β and AMP-activated protein kinase have been proposed. By contrast, anti-inflammatory cells, such as M2 macrophages, regulatory T cells and quiescent memory T cells, have lower glycolytic rates and higher levels of oxidative metabolism. Some anti-inflammatory agents might act by inducing, through activation of AMP-activated protein kinase, a state akin to pseudo-starvation. Altered metabolism may thus participate in the signal-directed programs that promote or inhibit inflammation.

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Figure 1: Central metabolic pathways involved in the Warburg effect in tumour cells and inflammatory cells.
Figure 2: Metabolic changes in TLR4-activated M1 macrophages.
Figure 3: Metabolic regulation of M2 macrophages and TH17 cells.
Figure 4: Regulation of AMPK by drugs, including anti-inflammatory drugs, and the principal metabolic pathways it regulates.

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Acknowledgements

Work in the D.G.H. laboratory is supported by the Wellcome Trust and Cancer Research UK. Work in the L.O.N. laboratory is supported by Science Foundation Ireland and the European Research Council.

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O'Neill, L., Hardie, D. Metabolism of inflammation limited by AMPK and pseudo-starvation. Nature 493, 346–355 (2013). https://doi.org/10.1038/nature11862

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