The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance (Nat Med, 2011, doi:10.1038/nm.2279)

報告日期: 2011/03/29
報告時間: 15:10/16:00
報告學生: 楊秀菊 (英文報告)
講評老師: 蔡曜聲

Full text:

The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance
Bolormaa Vandanmagsar. Yun-Hee Youm, Anthony Ravussin, Jose E Galgani, Krisztian Stadler, Randall L Mynatt, Eric Ravussin, Jacqueline M Stephens and Vishwa Deep Dixit
Nature Medicine, 2011, 17: 179-188
Speaker: 楊秀菊
Commentator:  Dr. 蔡曜聲
Date: 29 Mar, 2011    15:10~16:00
Place: Room 602
The innate immune system is the first line to against the microbial pathogens. The pathogen-recognition receptors (PRR) sense the foreign molecules (pathogen- associated molecular patterns, PAMP) and danger signals (danger-associated molecular patterns) from tissue damage and wound repair to cause the production of pro-inflammatory cytokines, such as IL-1β and IL-18. NLRP3 inflammasome is one of PRRs in the cytoplasm and is known to be activated by diverse substances, including pore-forming toxins, extracellular ATP, viral DNA, gout-associated uric acid crystals, silica, asbestos and amyloid-β. Here the authors demonstrated that NLRP3 inflammasome cause the obesity-induced inflammation and performed the relation between NLRP3 inflammasome and insulin resistance. They found that the caloric limited mice had the significant reduce in the gene level of IL-1β, NLRP3 and PYCARD compare to ad libitum control. Conversely, they detected the lower IL-18 production in the NLRP3-/- group compare to wild-type control when they were treated with high-fat diet. The insulin and glucose tolerance tests (ITT and GTT) have also shown the decrease in the NLRP3-/- group compare to wild-type control after high-fat diet treatment. The results suggested that the importance of NLRP3 inflammasome in glucose homeostasis. Macrophages as a scavenger clean the free fatty acids and sense the ceramide that is a product of fatty acids in adipose tissue. The authors found also the increase of IL10 and Arg1( favor to type 2 macrophage) and decrease of TNF-α, Nos2, Ccl20 and CXCL11(favor to type 1 macrophage) in NLRP3-/- group compare to wild-type control in visceral fat tissue. To analyze the CD4 and CD8 population, NLRP3-/- group have fewer cell number than control group, but there is no significant difference in Treg cells. Conversely, NLRP3-/- group have more cell number of CD4+ and CD8+ than control group in subcutaneous fat tissue, but the IFN-γproduction is lower. The data show that in the absence of NLRP3 inflammasome may lower macrophage-T cell activation, that participate in sustaining chronic inflammation in the adipose tissue.
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