Macrophage HIF-2α suppresses NLRP3 inflammasome activation and alleviates insulin resistance

• DOI: 10.1016/j.celrep.2021.109607
• Publication Date: 2021-08-24T14:49:25Z
• Authors: Xiaopeng Li; Xiujuan Zhang; Jialin Xia; Linqi Zhang; Bo Chen; Guan Lian; Chuyu Yun; Juan Yang; Yu Yan; Pengcheng Wang; Xuemei Wang; Bo Liu; Huiying Liu; Hui Liang; Yanli Pang; Xian Wang; Changtao Jiang
• Keywords: 0301 basic medicine; QH301-705.5; Inflammasomes; Macrophages; macrophage; Lipid Metabolism; 3. Good health; Mice; 03 medical and health sciences; EPAS1; NLR Family, Pyrin Domain-Containing 3 Protein; Basic Helix-Loop-Helix Transcription Factors; Animals; Humans; hypoxia inducible factor 2; Biology (General); Insulin Resistance; Cpt1a; FG-4592; fatty acid oxidation

The interrelation between hypoxia and immune response has pivotal roles in the pathogenesis of chronic metabolic diseases. However, role macrophage HIF-2α NLRP3 inflammasome activation remains unclear. Here, we show that deficiency macrophages results excessive a manner dependent on CPT1A-mediated enhancement fatty acid oxidation (FAO). Mechanistically, binds directly to Cpt1a promoter is involved regulation H3K27me3 methylation during activation. Myeloid-specific Hif2α knockout mice exhibit exacerbated insulin resistance increased macrophages. Overexpression gene or stabilization protein by FG-4592 ameliorates reduces Taken together, our suggest inhibits FAO-mediated alleviates resistance.