脂肪组织重塑和胰岛素抵抗密切相关，其主要特征是炎性巨噬细胞浸润和局部组织缺氧。我们前期在C57BL/6小鼠中发现高脂可诱导巨噬细胞缺氧诱导因子2α（HIF2α）和炎症因子表达上调，而巨噬细胞HIF2α敲除（HIF2αCKO）可改善高脂诱导的胰岛素抵抗、脂肪细胞肥大，并下调NLRP3的mRNA表达。提示巨噬细胞HIF2α可能通过NLRP3炎症小体调节脂肪组织重塑。本课题拟解决以下科学问题：（1）利用HIF2αCKO小鼠高脂胰岛素抵抗模型，阐明巨噬细胞HIF2α对脂肪组织重塑的影响；（2）通过改变HIF2α和NLRP3水平，利用骨髓来源巨噬细胞（BMDMs）和3T3L1细胞共培养，探讨HIF2α和NLRP3对脂肪细胞重塑的影响。利用JASPAR软件和染色质免疫共沉淀（ChIP），探索HIF2α调控NLRP3的机制。为深入理解胰岛素抵抗的发病机制奠定基础，也为肥胖和胰岛素抵抗治疗提供潜在靶点。

Adipose tissue remodeling is closely related to insulin resistance, and its main features are inflammatory macrophage infiltration and local tissue hypoxia. We have previously found that high-lipid-induced macrophage hypoxia-inducible factor 2α (HIF2α) and inflammatory factor expression are up-regulated in C57BL/6 mice, while macrophage HIF2α knockout (HIF2αCKO) improves high-fat-induced insulin resistance, and adipocytes hypertrophy, and down-regulate mRNA expression of NLRP3. It is suggested that macrophage HIF2α may regulate adipose tissue remodeling through NLRP3 inflammasome. This project aims to solve the following scientific problems: (1) using the high-fat insulin resistance model of HIF2αCKO mice to elucidate the effect of macrophage HIF2α on adipose tissue remodeling; (2) using bone marrow-derived macrophages by changing HIF2α and NLRP3 levels (BMDMs) and 3T3L1 cells were co-cultured to investigate the effects of HIF2α and NLRP3 on adipocyte remodeling. The mechanism by which HIF2α regulates NLRP3 was explored using JASPAR software and chromatin immunoprecipitation (ChIP). This study will lay a foundation for understanding the pathogenesis of insulin resistance, and to provide potential targets for obesity and insulin resistance treatment.