DIM调控Nrf2/HO-1信号通路和肠道菌群在儿童肥胖中的作用和机制研究

儿童肥胖是目前全世界儿童的主要健康问题。儿童肥胖会明显增加成年后慢性病的发病风险。3,3’-二吲哚甲烷(DIM)是一种广泛存在于十字花科蔬菜中的生物活性化合物,其在氧化应激和炎症反应中发挥重要作用。慢性低度炎症与肠道菌群失调以及肥胖都密切相关。饮食因素是肠道菌群功能非常关键地调节因素。然而DIM在调控肠道菌群失调以及在儿童肥胖发生中的作用并不明确。我们在预实验中发现DIM干预小鼠脂肪含量明显减少。为进一步验证假设我们在已经成功构建的菌群人源化HFA小鼠模型基础上,将采用肠道菌群测序、分子生物学等技术手段，通过分子、细胞和动物水平探讨DIM对Nrf2/HO-1通路和肠道菌群的影响以及在儿童肥胖发生中的作用机制。通过上述研究,为深入理解DIM及肠道菌群地变化在儿童肥胖发生发展中的作用机理提供理论依据,并可望为儿童肥胖预防和治疗提供新的靶点和途径。

Childhood obesity is becoming a serious problem in many countries. Obese children are more likely to become overweight and obese adults. Obesity in childhood is a potential risk for chronic diseases in later life. 3,3'-diindolylmethane (DIM) is one of the best-characterized and most abundant bioactive compounds found in commonly consumed crucifers. It plays a key role in regulating oxidative stress and inflammatory response, but its role in affecting gut microbiota disorder is still unclear. The gut microbiota play an important role in various biological processes. The relationship between gut microbiota and childhood obesity is still poorly understood. In addition, our preliminary data showed DIM intervention significantly reduced the fat content of mice. To this end, we hypothesized that DIM may play a role in the pathogenesis of childhood obesity by regulating the Nrf2/HO-1 signaling pathway and alteration of intestinal flora. To verify this hypothesis, we will explore the effect of DIM on childhood obesity from the aspects of molecular, cellular, and animal levels, and will use intestinal epithelial cells, gene knockout animal models, and human -flora -associated (HFA) mice models by gut microbiota sequencing, gas chromatography, and immunohistochemistry. This study will lay a foundation for revealing the role of gut microbiota disorder in the development of childhood obesity from the new perspective of DIM, and provide new ideas for the prevention and treatment of childhood obesity.