IL-38对肥胖相关性炎症和胰岛素抵抗的调控及其机制的研究

WHO警告肥胖是全球引起死亡的第五大风险。肥胖患者均不同程度地存在炎症和胰岛素抵抗。IL-38是新近发现的一种抗炎因子，我们在已经构建的肥胖小鼠模型中，观察到IL-38可以降低脂肪组织和血清中TNF-α和IL-6等炎症因子的表达，并增加小鼠葡萄糖耐量和胰岛素敏感性。提示IL-38对肥胖诱导的炎症和胰岛素抵抗可能有重要的调控作用。在此发现基础上，为进一步验证并明确IL-38调控肥胖炎症和胰岛素信号的分子机制，拟综合运用多种实验技术，如基因敲除和细胞转染等，在整体水平探讨①IL-38与临床肥胖症发生发展的相关性，以及IL-38在人体脂肪组织中的表达差异和对脂肪组织炎症状态的影响。②动物水平研究IL-38对脂肪组织炎症和胰岛素信号的作用及具体机制。③体外细胞实验确定IL-38调控肥胖炎症和胰岛素抵抗的可能信号通路或关键性的靶点分子。结果将为临床上肥胖及其相关疾病的治疗提供新思路。

WHO warns that obesity is the fifth biggest risk of death worldwide. Obesity patients have varying degrees of inflammation and insulin resistance. IL-38 is a newly anti-inflammatory factor. In the established obese mouse model, we observed that IL-38 can reduce the expression of inflammatory factors such as TNF-α and IL-6 in adipose tissue and serum, and increase glucose tolerance and insulin sensitivity in mice. It suggests that IL-38 may play an important regulatory role in obesity-induced inflammation and insulin resistance. Based on this finding, in order to further validate and clarify the molecular mechanism of IL-38 regulation of obesity inflammation and insulin signaling, it is proposed to use a variety of experimental techniques, such as gene knockout and cell transfection, to explore the overall level (1) IL-38 is clinically associated with the development of obesity, and the differential expression of IL-38 in human adipose tissue and its influence on the inflammatory state of adipose tissue. (2) The role of IL-38 in adipose tissue inflammation and insulin signaling and its specific mechanism at animal level. (3) In vitro cell assays identify possible signaling pathways or key target molecules for IL-38 regulation of obesity and insulin resistance. The results will provide new ideas for the treatment of clinical obesity and related diseases.