| First Author | Wen H | Year | 2011 |
| Journal | Nat Immunol | Volume | 12 |
| Issue | 5 | Pages | 408-15 |
| PubMed ID | 21478880 | Mgi Jnum | J:172610 |
| Mgi Id | MGI:5008358 | Doi | 10.1038/ni.2022 |
| Citation | Wen H, et al. (2011) Fatty acid-induced NLRP3-ASC inflammasome activation interferes with insulin signaling. Nat Immunol 12(5):408-15 |
| abstractText | High-fat diet (HFD) and inflammation are key contributors to insulin resistance and type 2 diabetes (T2D). Interleukin (IL)-1beta plays a role in insulin resistance, yet how IL-1beta is induced by the fatty acids in an HFD, and how this alters insulin signaling, is unclear. We show that the saturated fatty acid palmitate, but not unsaturated oleate, induces the activation of the NLRP3-ASC inflammasome, causing caspase-1, IL-1beta and IL-18 production. This pathway involves mitochondrial reactive oxygen species and the AMP-activated protein kinase and unc-51-like kinase-1 (ULK1) autophagy signaling cascade. Inflammasome activation in hematopoietic cells impairs insulin signaling in several target tissues to reduce glucose tolerance and insulin sensitivity. Furthermore, IL-1beta affects insulin sensitivity through tumor necrosis factor-independent and dependent pathways. These findings provide insights into the association of inflammation, diet and T2D. |
