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A role for the NLRP3 inflammasome in metabolic diseases—did Warburg miss inflammation?

Abstract

The inflammasome is a protein complex that comprises an intracellular sensor (typically a Nod-like receptor), the precursor procaspase-1 and the adaptor ASC. Inflammasome activation leads to the maturation of caspase-1 and the processing of its substrates, interleukin 1β (IL-1β) and IL-18. Although initially the inflammasome was described as a complex that affects infection and inflammation, subsequent evidence has suggested that inflammasome activation influences many metabolic disorders, including atherosclerosis, type 2 diabetes, gout and obesity. Another feature of inflammation in general and the inflammasome specifically is that the activation process has a profound effect on aerobic glycolysis (the 'Warburg effect'). Here we explore how the Warburg effect might be linked to inflammation and inflammasome activation.

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Figure 1: A model for the pathogenesis of type 2 diabetes involving adipose tissue, the pancreas and NLRP3.
Figure 2: Metabolic fluxes, NLRP3 and IL-1β.

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Acknowledgements

Supported by the US National Institutes of Health (R37-AI029564-17 and CA-156330-01 to J.P.-Y.T.), the Cancer Research Institute (H.W.) and Science Foundation Ireland (L.A.J.O.).

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Correspondence to Jenny P-Y Ting or Luke A J O'Neill.

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Wen, H., Ting, JY. & O'Neill, L. A role for the NLRP3 inflammasome in metabolic diseases—did Warburg miss inflammation?. Nat Immunol 13, 352–357 (2012). https://doi.org/10.1038/ni.2228

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