内质网（Endoplasmic Reticulum，ER）是细胞中维持蛋白质和脂类内稳态的重要细胞器。当细胞受到外界刺激时，大量错误折叠蛋白堆积在ER中，从而激活未折叠蛋白反应（Unfolded Protein Response，UPR）来调控细胞内稳态。肥胖是非酒精性脂肪肝的主要诱因，临床发现肥胖人群的脂肪组织和非酒精性脂肪肝人群肝脏中UPR均被激活，然而对于UPR能否跨组织以及如何跨组织影响两者之间的信号传导仍不清楚。前期数据表明，UPR激活状态的成熟脂肪细胞能诱导肝细胞产生UPR。本课题将利用脂肪细胞和肝细胞，针对UPR中最保守支路IRE1α-XBP1，阐明其跨细胞信号传导分子机制。一方面通过对供体脂肪细胞分泌的活性物质和自身分泌机制进行探讨分析，明确UPR信号传导媒介及产生机制；另一方面通过受体肝细胞全转录组学检测，深入挖掘信号接收机制，并探讨其生理学意义。

ER (Endoplasmic Reticulum) plays an important role in maintaining homeostasis of cellular proteins and lipids. When cells are exposed to stresses that lead to protein misfolding and accumulation in the ER lumen, UPR (Unfolded Protein Response) is activated to regulate cellular homeostasis. Obesity is the main cause of NAFLD (Nonalcoholic Fatty Liver Disease), and the interaction between obesity and NAFLD has become a research focus. Clinical studies show that the UPR is activated in the adipose tissue of obese people and the liver tissue of NAFLD patients. Although the UPR is closely related to obesity and NAFLD, it remains elusive how it influences the interaction between these two tissues. Our preliminary experiment showed that the UPR-activated adipocytes could induce UPR in hepatocytes. We will study the mechanism of intercellular UPR transmission by utilizing mature adipocytes and hepatocytes focusing on IRE1a-XBP1, the most conserved branch of the UPR. On the one hand, we will determine the functional elements secreted by adipocytes that transmit the intercellular UPR signaling and the secretory mechanism; on the other hand, we will identify the receiving signaling pathway in hepatocytes through analysis of transcriptomics and research on its physiological significance.