| First Author | Li X | Year | 2021 |
| Journal | Cell Rep | Volume | 36 |
| Issue | 8 | Pages | 109607 |
| PubMed ID | 34433035 | Mgi Jnum | J:330772 |
| Mgi Id | MGI:6765717 | Doi | 10.1016/j.celrep.2021.109607 |
| Citation | Li X, et al. (2021) Macrophage HIF-2alpha suppresses NLRP3 inflammasome activation and alleviates insulin resistance. Cell Rep 36(8):109607 |
| abstractText | The interrelation between hypoxia and immune response has pivotal roles in the pathogenesis of chronic metabolic diseases. However, the role of macrophage HIF-2alpha in NLRP3 inflammasome activation remains unclear. Here, we show that deficiency of HIF-2alpha in macrophages results in excessive activation of the NLRP3 inflammasome in a manner dependent on CPT1A-mediated enhancement of fatty acid oxidation (FAO). Mechanistically, HIF-2alpha binds directly to the Cpt1a promoter and is involved in the regulation of H3K27me3 methylation during NLRP3 inflammasome activation. Myeloid-specific Hif2alpha knockout mice exhibit exacerbated insulin resistance and increased activation of NLRP3 inflammasome in macrophages. Overexpression of the Hif2alpha gene or stabilization of the protein by FG-4592 ameliorates insulin resistance and reduces NLRP3 inflammasome activation in macrophages. Taken together, our results suggest that macrophage HIF-2alpha inhibits FAO-mediated activation of the NLRP3 inflammasome and alleviates insulin resistance. |
