Journal article
IL-18 Production from the NLRP1 Inflammasome Prevents Obesity and Metabolic Syndrome
AJ Murphy, MJ Kraakman, HL Kammoun, D Dragoljevic, MKS Lee, KE Lawlor, JM Wentworth, A Vasanthakumar, M Gerlic, LW Whitehead, L Dirago, L Cengia, RM Lane, D Metcalf, JE Vince, LC Harrison, A Kallies, BT Kile, BA Croker, MA Febbraio Show all
Cell Metabolism | CELL PRESS | Published : 2016
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 concen..
View full abstractGrants
Awarded by Australian Cancer Research Foundation
Funding Acknowledgements
We thank L. Scott, R. Crawley, and K. Hay for outstanding animal husbandry. We also thank Prof A. Roberts (The Walter and Eliza Hall Institute) for assistance with mouse studies. This work was supported by Project Grants (637367, 1002426, 1051210, 1057815), Program Grants (461219, 363652, 1016647), Fellowships (S.L.M., B.T.K., M.A.F., A.J.M., J.E.V.), and an Independent Research Institutes Infrastructure Support Scheme Grant (361646) from the Australian National Health and Medical Research Council (NHMRC); the Australian Phenomics Network, the Australian Cancer Research Foundation, and a Victorian State Government Operational Infrastructure Support Grant. A.J.M was also supported by a future leader fellowship from the National Heart Foundation, and a Viertel award from Diabetes Australia Research Trust Australia.