IL-18 production from the NLRP1 inflammasome prevents obesity and metabolic syndrome
- Author(s)
- Murphy, Andrew J; Kraakman, Michael J; Kammoun, Helene L; Dragoljevic, Dragana; Lee, Man K S; Lawlor, Kate E; Wentworth, John M; Vasanthakumar, Ajithkumar; Gerlic, Motti; Whitehead, Lachlan W; DiRago, Ladina; Cengia, Louise; Lane, Rachael M; Metcalf, Donald; Vince, James E; Harrison, Leonard C; Kallies, Axel; Kile, Benjamin T; Croker, Ben A; Febbraio, Mark A; Masters, Seth L;
- Details
- Publication Year 2016-01-12,Volume 23,Issue #1,Page 155-164
- Journal Title
- Cell Metabolism
- Publication Type
- Journal Article
- Abstract
- Summary Interleukin-18 (IL-18) is activated by Caspase-1 in inflammasome complexes and has anti-obesity effects; however, it is not known which inflammasome regulates this process. We found that mice lacking the NLRP1 inflammasome phenocopy mice lacking IL-18, with spontaneous obesity due to intrinsic lipid accumulation. This is exacerbated when the mice are fed a high-fat diet (HFD) or a high-protein diet, but not when mice are fed a HFD with low energy density (high fiber). Furthermore, mice with an activating mutation in NLRP1, and hence increased IL-18, have decreased adiposity and are resistant to diet-induced metabolic dysfunction. Feeding these mice a HFD further increased plasma IL-18 concentrations and strikingly resulted in loss of adipose tissue mass and fatal cachexia, which could be prevented by genetic deletion of IL-18. Thus, NLRP1 is an innate immune sensor that functions in the context of metabolic stress to produce IL-18, preventing obesity and metabolic syndrome.
- Publisher
- Cell Press
- Research Division(s)
- Inflammation; Population Health And Immunity; Systems Biology And Personalised Medicine; Cancer And Haematology; Immunology; Chemical Biology
- PubMed ID
- 26603191
- Publisher's Version
- https://doi.org/http://dx.doi.org/10.1016/j.cmet.2015.09.024
- NHMRC Grants
- NHMRC/637367, NHMRC/1002426, NHMRC/1051210, NHMRC/1057815, NHMRC/461219, NHMRC/1016647,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2015-11-19 02:00:40
Last Modified: 2019-04-01 08:56:50