脂肪组织的代谢功能和慢性炎症反应在胰岛素抵抗和2型糖尿病（T2DM）发生发展中发挥重要作用。过氧化物酶增殖物激活受体γ（PPARγ）是调控脂肪组织功能最为关键的转录因子，其激动剂是治疗2型糖尿病的临床用药。最新的研究发现，II类反式作用因子（CIITA）介导的MHCII的表达在肥胖诱导的脂肪炎症中起着重要作用，干预MHCII能够增强胰岛素的敏感性。我们前期的研究发现，INF-γ通过诱导CIITA的表达抑制了脂肪细胞的分化作用，同时INF-γ介导CIITA的表达能够抑制PPAR反应元件（PPRE）转录活性。因此我们假设：在脂肪组织及细胞中IFN-γ通过CIITA调控了PPAR-γ的转录活性进而在胰岛素抵抗和T2DM发生发展起到重要的作用。我们希望通过本课题的研究揭开炎症应激抑制PPARγ转录引起脂肪细胞代谢紊乱的表观遗传机制，并为临床防治2型糖尿病提供可能的药物干预新靶点。

Metabolic function and chronic inflammatory responses in adipose tissue play an important role in the development of insulin resistance and type 2 diabetes mellitus (T2DM). Peroxisome proliferator-activated receptor γ (PPARγ) is the most critical transcription factor in regulating adipose tissue function. PPARγ agonists are used clinically to treat type 2 diabetes.The latest study found that class II transactivator (CIITA) mediated MHCII expression plays an important role in obesity induced inflammation in adipose, the disruption of which can enhance insulin sensitivity. Our previous studies have found that INF-γ induced the expression of CIITA ,which inhibited adipocyte differentiation. While INF-γ mediated the expression of CIITA could repress PPAR response element (PPRE) transcriptional activity. Therefore, we hypothesized that IFN-γ could regulate PPAR-γ transcription activity by CIITA in adipocytes and thus play an important role in the development of insulin resistance and T2DM. Our goal is to investigate the epigenetic mechanism that contributes to PPARγ repression and disruption of metabolic homeostasis in adipocytes in response to inflammation and to provide novel insight to the development of potential prevention and intervention strategies for type 2 diabetes.