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Turning off the inflammatory, but not the metabolic, flames

Nature Medicine volume 19, pages 265–267 (2013)Cite this article

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Metabolically driven, chronic, low-grade inflammation has a crucial role in the pathogenesis of obesity and type 2 diabetes, and multiple stress-signaling cascades link insulin resistance and the immune response. An approved immunomodulatory drug is now shown to inhibit the kinases IKKε and TBK1, suppress inflammation and improve metabolic homeostasis in mouse models of obesity (pages 313–321).

Since the discovery 20 years ago that the proinflammatory cytokine tumor necrosis factor-α (TNF-α) is secreted from obese adipose tissue, an array of inflammatory mediators that are produced from various metabolically active tissues and from resident immune cells within these tissues have now been identified and shown to cause insulin resistance and metabolic deterioration in obesity1,2. Although the temporal and spatial order of these metabolically driven immunological alterations and the cell types involved remain an active area of investigation, it is clear that the low-grade, chronic inflammation, or 'metaflammation', seen in obesity is an important factor in disease pathogenesis3. Metabolic inflammation is a distinct phenomenon from the classical inflammation described by the Roman physician Aulus Cornelius Celsus, as it lacks calor, dolor, rubor and tumor and is not accompanied by increased basal energy expenditure. In other words, metaflammation, which is orchestrated by nutritional and metabolic cues, is 'cold', whereas classical inflammation, which is driven by pathogens and injury, is 'hot'.

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Figure 1: Signaling pathways involved in classical inflammation and metaflammation.

Marina Corral

Change history

  • 22 March 2013

     In the version of this article initially published, TBK1 was incorrectly referred to in a number of instances as TKB1. The error has been corrected in the HTML and PDF versions of the article.

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Authors and Affiliations

  1. Ediz S. Calay and Gökhan S. Hotamisligil are in the Department of Genetics and Complex Diseases and the Broad Institute of Massachusetts Institute of Technology and Harvard University, Harvard School of Public Health, Boston, Massachusetts, USA.,

    Ediz S. Calay & Gökhan S. Hotamisligil

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  1. Ediz S. Calay
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  2. Gökhan S. Hotamisligil
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Correspondence to Gökhan S. Hotamisligil.

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Calay, E., Hotamisligil, G. Turning off the inflammatory, but not the metabolic, flames. Nat Med 19, 265–267 (2013). https://doi.org/10.1038/nm.3114

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