期刊
CELL METABOLISM
卷 23, 期 1, 页码 155-164出版社
CELL PRESS
DOI: 10.1016/j.cmet.2015.09.024
关键词
-
资金
- Australian National Health and Medical Research Council (NHMRC) [361646]
- Australian Phenomics Network
- Australian Cancer Research Foundation
- Victorian State Government Operational Infrastructure Support Grant
- National Heart Foundation
- Diabetes Australia Research Trust Australia
- [637367]
- [1002426]
- [1051210]
- [1057815]
- [461219]
- [363652]
- [1016647]
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据