脂肪组织巨噬细胞（ATM）是肥胖状态下介导炎症反应的主要细胞。深入研究并阐明ATM对肥胖及肥胖2型糖尿病的具体调控机制，已经成为治疗由肥胖引起的代谢综合征的重要基础 。我们初步发现与正常人的脂肪组织巨噬细胞(ATM)相比，肥胖、肥胖2型糖尿病患者的ATM中Stk24激酶表达量显著下调，高脂饮食HFD诱导小鼠的ATM中Stk24表达也明显下降。而Stk24在巨噬细胞中敲除显著加重HFD诱导的胰岛素抵抗和主要代谢器官的组织破坏、脂肪沉积及胶原沉积等病理变化。本项目拟在此基础上利用小鼠模型，免疫印迹、免疫共沉淀和免疫荧光共聚焦等技术明确Stk24在高脂饮食诱导的肥胖及代谢综合征中的作用及其具体作用机制。同时明确Stk24在肥胖和肥胖2型糖尿病表达下调的分子机制。本研究的完成将进一步丰富和完善肥胖及相关代谢综合征发生的调控机制，为肥胖及其相关代谢综合征的临床治疗和药物开发提供新的靶点。

Obesity has become a more and more serious global problem that has plagued people's lives. It produces a series of chronic inflammation reactions which leads to insulin resistance and even type 2 diabetes (T2D). Previous studies demonstrated that adipose tissue macrophages (ATMs) play an important role in the development of metabolic sydrome.The serine/threonine protein kinase 24 (Stk24) is a member of the serine/threonine kinase family and involved in the regulation of cell migration, apoptotic protease-dependent or non-dependent apoptosis. In the adipose tissue macrophages (ATM) from obesity and obese Type 2 diabetes patients, we found a significant downregulation of Stk24 expression level compared to the ATM from lean control subjects. In the high fat diet (HFD) induced obesity model, The LysmCre Stk24f/f mice developed more severe insulin resistance and a series of relative pathological changes compared to the Stk24f/f. We will further clarify the role of Stk24 in obesity-induced inflammation and insulin resistance and the related- regulatory mechanism. Also, we will explore the underlined mechanisms by which HFD treatment inhibits the expression of Stk24 in ATM. The completion of this study will provide new ideas and potential targets for the clinical diagnosis and treatment of diet-induced metabolic dysfunction.