AHR在代谢健康型肥胖肠道菌群-胰岛免疫稳态中的作用及机制研究

代谢健康型肥胖（MHO）是肥胖但代谢指标持续正常的一种特殊表型。胰岛功能是否能代偿决定了肥胖者血糖能否正常。项目前期表明，MHO存在类似2型糖尿病的免疫紊乱和代谢性炎症，且芳香烃受体（AhR）通路表现出显著差异。最近AhR在肠道菌群、免疫稳态、代谢调控中的作用受到越来越多重视。已知不同手段干预AhR通路能导致小鼠在发生肥胖后代谢结局截然不同，但具体机制尚不清楚。作为受环境配体调控的转录因子，AhR已被证实是肠道菌群与免疫稳态的基本传感器。有理由假设，AhR可能通过调控机体免疫与肠道菌群的相互作用影响宿主代谢。而AhR-肠道菌群的交互作用是否能影响MHO的胰岛免疫-代谢稳态尚未见报道。基于前期研究及文献支持，项目旨在探讨肥胖代谢表型差异的深层次机制，验证肠道菌群-胰岛免疫对话在肥胖代谢转归中的作用，研究AhR通路作用机制及针对性干预策略，为肥胖及其相关代谢紊乱的干预提供新的思路和靶点。

Metabolically healthy obesity (MHO) is a special phenotype of obesity whose metabolic index appears continuously normal. Whether the islets function could compensate or not determines whether the glucose homeostasis could be normal. Our previous study indicated that mho had immune disorder and metabolic inflammation similar to type 2 diabetes, while the aromatic hydrocarbon receptor (AhR) pathway shows significant difference. In recent years, the role of AhR in endocrine disruptors and immune homeostasis has been drawing more and more attention. Different interventions of AhR pathway can lead to entirely different metabolic outcomes in obese models, but the specific mechanism is not clear. As a transcription factor regulated by xenobiotic ligands, AhR has been proved an essential sensor between gut microbiota and immune homeostasis. It is reasonable to assume that AhR can affect host metabolism by regulating the interaction between immunity and gut microbiota. Moreover, there was no report regarding whether the AhR-gut microbiota interaction could affect the immune-metabolic homeostasis in MHO. Based on our previous study and related literatures, this study makes efforts to discuss the underlying mechanism of differential metabolic outcomes in obesity, to verify the role of gut microbiota and AhR signaling, aiming to provide new ideas and targets for intervention of obesity related metabolic disorder.