| Title : Macrophage CGI-58 deficiency activates ROS-inflammasome pathway to promote insulin resistance in mice - Miao_2014_Cell.Rep_7_223 |
| Author(s) : Miao H , Ou J , Ma Y , Guo F , Yang Z , Wiggins M , Liu C , Song W , Han X , Wang M , Cao Q , Chung BH , Yang D , Liang H , Xue B , Shi H , Gan L , Yu L |
| Ref : Cell Rep , 7 :223 , 2014 |
| Abstract : Overnutrition activates a proinflammatory program in macrophages to induce insulin resistance (IR), but its molecular mechanisms remain incompletely understood. Here, we show that saturated fatty acid and lipopolysaccharide, two factors implicated in high-fat diet (HFD)-induced IR, suppress macrophage CGI-58 expression. Macrophage-specific CGI-58 knockout (MaKO) in mice aggravates HFD-induced glucose intolerance and IR, which is associated with augmented systemic/tissue inflammation and proinflammatory activation of adipose tissue macrophages. CGI-58-deficient macrophages exhibit mitochondrial dysfunction due to defective peroxisome proliferator-activated receptor (PPAR)gamma signaling. Consequently, they overproduce reactive oxygen species (ROS) to potentiate secretion of proinflammatory cytokines by activating NLRP3 inflammasome. Anti-ROS treatment or NLRP3 silencing prevents CGI-58-deficient macrophages from oversecreting proinflammatory cytokines and from inducing proinflammatory signaling and IR in the cocultured fat slices. Anti-ROS treatment also prevents exacerbation of inflammation and IR in HFD-fed MaKO mice. Our data thus establish CGI-58 as a suppressor of overnutrition-induced NLRP3 inflammasome activation in macrophages. |
| ESTHER : Miao_2014_Cell.Rep_7_223 |
| PubMedSearch : Miao_2014_Cell.Rep_7_223 |
| PubMedID: 24703845 |
Miao H, Ou J, Ma Y, Guo F, Yang Z, Wiggins M, Liu C, Song W, Han X, Wang M, Cao Q, Chung BH, Yang D, Liang H, Xue B, Shi H, Gan L, Yu L (2014)
Macrophage CGI-58 deficiency activates ROS-inflammasome pathway to promote insulin resistance in mice
Cell Rep
7 :223
Miao H, Ou J, Ma Y, Guo F, Yang Z, Wiggins M, Liu C, Song W, Han X, Wang M, Cao Q, Chung BH, Yang D, Liang H, Xue B, Shi H, Gan L, Yu L (2014)
Cell Rep
7 :223