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https://hdl.handle.net/2440/121743
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Type: | Journal article |
Title: | IL-18 production from the NLRP1 inflammasome prevents obesity and metabolic syndrome |
Author: | Murphy, A.J. Kraakman, M.J. Kammoun, H.L. Dragoljevic, D. Lee, M.K.S. Lawlor, K.E. Wentworth, J.M. Vasanthakumar, A. Gerlic, M. Whitehead, L.W. Dirago, L. Cengia, L. Lane, R.M. Metcalf, D. Vince, J.E. Harrison, L.C. Kallies, A. Kile, B.T. Croker, B.A. Febbraio, M.A. et al. |
Citation: | Cell Metabolism, 2016; 23(1):155-164 |
Publisher: | Cell Press; Elsevier |
Issue Date: | 2016 |
ISSN: | 1550-4131 1932-7420 |
Statement of Responsibility: | Andrew J. Murphy, Michael J. Kraakman, Helene L. Kammoun, Dragana Dragoljevic, Man K.S. Lee ... Benjamin T. Kile ... et al. |
Abstract: | 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. |
Keywords: | Apoptosis Regulatory Proteins |
Rights: | © 2016 Elsevier Inc. |
DOI: | 10.1016/j.cmet.2015.09.024 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/361646 http://purl.org/au-research/grants/nhmrc/637367 http://purl.org/au-research/grants/nhmrc/1002426 http://purl.org/au-research/grants/nhmrc/1051210 http://purl.org/au-research/grants/nhmrc/1057815 http://purl.org/au-research/grants/nhmrc/461219 http://purl.org/au-research/grants/nhmrc/363652 http://purl.org/au-research/grants/nhmrc/1016647 |
Published version: | http://dx.doi.org/10.1016/j.cmet.2015.09.024 |
Appears in Collections: | Aurora harvest 8 Medical Sciences publications |
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