IL-18 Production from the NLRP1 Inflammasome Prevents Obesity and Metabolic Syndrome

 Murphy et al., (2016) Cell Metabolism 23, 155-164

Speaker: Chih-Yu Huang (黃智裕)             )                 Time: 15:10-16:00, Mar 16, 2016

Commentator: Dr. Yao-Sheng Tsai (蔡曜聲)      )    Place: Room 601

Abstract

  IL-18 is known for its role in initiating immune responses after being processed by caspase-1 in inflammasome complexes. IL-18 is also indicated to play roles in regulating energy homeostasis and causing metabolic diseases ^[1]. Loss of IL-18 results in exacerbated adiposity and insulin resistance ^{[2] [3]}, the phenotypes of obesity, which suggestings that IL-18 has anti-obesity effects. However, which inflammasome regulates this process is still unknown. Here, the authors found that in consistent with mice lacking IL-18, mice lacking NLRP1 inflammasome develop spontaneous obesity due to lipid accumulation and fail to properly regulate blood glucose, insulin, and leptin levels that resemblessimilar to those observed in the metabolic syndrome. This is evenMouse obesity and metabolic syndrome are aggravated worsened when the mice are fed with a high-fat diet (HFD) or a high-protein diet, but not HFD with high fiber content. These abnormalities are reversed in mice with an activating mutation in NLRP1 (Nlrp1^MUT), with the increase in IL-18 level. Nlrp1^MUT Feeding these mice fed with a HFD further increases the IL-18 levelfurther increases the IL-18 level. UnfortunatelySurprisingly, the increase of IL-18 due to HFD is fatal for these mice with a great loss of adipose tissue and cachexia, but thiswhich could be prevented by IL-18 deletion. In conclusion, the authors demonstrated that NLRP1 functions as a sensor in detecting increased energy intake to produce maintain IL-18 homeostasis for preventing obesity and metabolic syndrome.

References

1.     Febbraio, M.A. (2014). Role of interleukins in obesity: implications for metabolic disease. Trends Endocrinol. Metab. 25, 312-319.

2.     Esposito et al. (2002). Weight loss reduces interleukin-18 levels in obese women. J. Clin. Endocrinol. Metab. 87, 3864-3866.

1.Hung et al. (2005). Elevated interleukin-18 levels are associated with the metabolic syndrome independent of obesity and insulin resistance. Arterioscler. Thromb. Vasc. Biol. 25, 1268-1273.

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