| First Author | Murphy AJ | Year | 2016 |
| Journal | Cell Metab | Volume | 23 |
| Issue | 1 | Pages | 155-64 |
| PubMed ID | 26603191 | Mgi Jnum | J:232742 |
| Mgi Id | MGI:5780014 | Doi | 10.1016/j.cmet.2015.09.024 |
| Citation | Murphy AJ, et al. (2016) IL-18 Production from the NLRP1 Inflammasome Prevents Obesity and Metabolic Syndrome. Cell Metab 23(1):155-64 |
| abstractText | 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. |
