高脂饮食诱导的肥胖母孕鼠肠道微生态和瘦素变化对雄性子代TRAMP鼠前列腺癌自然进程的影响和作用机制

我们在面上项目（81272835）资助下，证实高脂饮食可激活IGF1-IR-PI3K-Akt信号通路促进前列腺癌侵袭和进展，发现“高脂喂养的肥胖孕母鼠可促进其雄性子代TRAMP鼠前列腺癌早发生”，提示母孕体代谢微环境状态可以影响子代前列腺癌的生物学行为和疾病进程。我们在TRAMP鼠模型上初步探索了瘦素水平的变化对AEBP1表达和PI3K-Akt信号通路的影响，同时发现高脂饮食可以改变母鼠及子代雄鼠的肠道微生物的组成。由此提出科学假说：高脂饮食诱发的母孕体代谢微环境状态通过肠道微生态和瘦素变化等因素影响雄性子代前列腺癌的生物学特性和自然进程。本项目拟在高脂饮食诱导的肥胖母孕鼠的雄性子代TRAMP鼠模型上，深入研究肠道微生态和瘦素变化对AEBP1和PTEN的作用以及调控PI3K-Akt信号通路的机制，阐述母体代谢微环境变化对雄性子代前列腺癌自然进程的影响，为前列腺癌预防提供新思路和理论。

Under the project funding of NSFC(81272835),We confirmed that high fat diet can activate the IGF1-IR-PI3K-Akt signaling pathway to promote the invasion and progression of prostate cancer. We also found an interesting phenomenon that " Obese pregnant rats fed by high fat diet can promote prostate cancer earlier in their male TRAMP offspring" which indicates that the metabolic microenvironment in maternal body can affect the biological behavior and process of prostate cancer in male offspring. We have investigated the effects of leptin levels on the expression of AEBP1 and PI3K-Akt signaling pathways in TRAMP models, also found that high fat diet can alter the gut microbiota of both pregnant rats and their male offsprings. A scientific hypothesis is put forward: the metabolic microenvironment state of maternal pregnancy fed by high fat diet can affects the biological characteristics and the natural process of male offspring prostate cancer through the factors of gut microbiota and leptin. This project intends to study the effect of gut microbiota and leptin on AEBP1 and PTEN and the mechanism of how to regulate the PI3K-Akt signaling pathway on the basis of expanded samples of obese pregnant rats and their male offspring of TRAMP rats. The effects of maternal metabolic microenvironment on the natural process of prostatic cancer in male offsprings will be discussed, thus to provide potential new ideas for the prevention of prostate cancer.