脂肪细胞来源A-FABP调控肠道干细胞分化及肠粘膜损伤修复的机制研究

肥胖相关的内脏脂肪堆积与炎症性肠病（inflammatory bowel diseases，IBDs）的发病有显著相关性。然而，脂肪组织及其分泌的代谢物/代谢调控物在肠道粘膜修复和IBDs发病中的生理病理作用还极少被研究。我们的前期工作发现：IBDs急性发作期血清中脂肪细胞来源的脂肪因子A-FABP含量显著升高；A-FABP参与调控肠道干细胞（intestinal stem cells，ISCs）中过氧化物酶体的活性。我们最新发表的工作证实：过氧化物酶体参与调控ISCs分化和肠粘膜修复。基于以上基础，本项目拟综合利用人类IBDs患者肠组织、小鼠溃疡性结肠炎和果蝇肠受损模型：揭示脂肪组织在肠粘膜修复和人类IBDs中的生理病理功能；阐明脂肪细胞来源A-FABP及其介导的脂代谢途径通过炎症反应和过氧化物酶体相关代谢途径调控ISCs分化和肠粘膜修复的分子机制；为治疗IBDs提供新的理论依据和靶点。

Obesity-related accumulation of visceral fat has been connected with human inflammatory bowel disease (IBDs). However, the physiological and pathological effects of adipose tissue and its secreted metabolites/metabolic regulators in intestinal mucous repair and IBDs have rarely been studied. Our preliminary data show that the adipocyte-secreted adipokine A-FABP significantly increases in the serum during IBDs acute attack stage; A-FABP plays a role in regulating the activity of peroxisomes in intestinal stem cells (ISCs) during the gut repair. Our newly published work demonstrates that peroxisomes are key regulators of ISCs differentiation and intestinal mucous repair after gut injury. Based on our previous work, this project intends to use intestinal tissue of IBDs patients, ulcerative colitis mouse, and gut damaged Drosophila models to reveal the physiological and pathological function of adipose tissue in intestinal mucous repair and human IBDs; to explore the underlying molecular mechanism of how adipocyte-secreted A-FABP and its mediated lipid metabolic pathways regulate ISCs differentiation and intestinal mucosal repair through modulation of inflammation response and peroxisome-mediated metabolisms; to provide new theoretical basis and targets for the treatment of IBDs.