肥胖是宿主自身基因和肠道微生物双重作用的结果，饮食诱导肠道菌群失衡是肥胖形成的重要因素。我们前期研究显示：高脂饮食宿主肠道菌群代谢黄酮类物质的活性降低，相应小分子产物DAT浓度下降；补充DAT则可减少其体重增长和白色脂肪累积。进一步的结果显示：DAT抑制肠炎小鼠的肠道和系统性炎症。转录组分析发现：DAT在广泛下调宿主炎症相关功能基因表达的同时活化Ⅰ型干扰素相关通路；提示DAT可能通过Ⅰ型干扰素通路减轻肥胖和相关代谢性炎症。目前，DAT在肥胖及慢性代谢性炎症中的作用及机制均未见报道。本课题拟以DAT调节宿主Ⅰ型干扰素通路为出发点，采用离体和在体模型明确Ⅰ型干扰素通路在DAT减轻脂肪炎症和肥胖中的作用，再挖掘和确证DAT调控Ⅰ型干扰素通路的关键蛋白；从整体、细胞和分子水平探讨DAT调控宿主Ⅰ型干扰素通路减轻肥胖及相关代谢性炎症的分子机制，以期为肥胖及相关代谢性炎症的防治新策略提供实验依据。

Abstract: Interactions of the gut microbiota and host genetics are involved in the development of obesity. The diet-induced imbalance of gut microbiota promotes obesity. Our previous studies suggested that the ability to degrade flavonoids by microbiota of host consuming high fat diet (HFD) was reduced and desaminotyrosine (DAT), a degradation product of flavonoids by bacteria, markedly reduced in HFD-fed mice. Interestingly, DAT-treated mice showed less body weight gain and less white adipose tissue accumulation. Moreover, our studies suggested that the metabolite of gut microbiota mitigated gut and systemic inflammation in mice with colitis. Further transcriptional data analysis implied that the major type I interferon-activated signaling pathways were enhanced in DAT-treated group. Previous studies suggested that DAT could protect host from virus infection through type I interferon signaling pathway. However, both the role of DAT in obesity and the mechanism involved have not been reported previously. In the project, we propose to confirm the role of type I interferon signaling pathway in the alleviation of obesity by DAT in vitro and in vivo, and then sieve the key protein or interaction in the regulation of type I interferon pathway by DAT to investigate the mechanism revealing the alleviation of obesity through the regulation of type I interferon signaling pathway by DAT. This project will provide new experimental evidences for the strategy to prevent and/or treat obesity and related metabolic inflammation.