高脂饮食对于肠道基因表现的影响

Effect of High Fat Diet on Intestinal Gene Expression in Hamster

摘要: 本研究透过次世代定序与大数据的分析，研究高脂饮食对仓鼠肠道组织基因表现。将16只仓鼠分成对照组和高脂组。在第12周将高脂组改摄取控制组饲料，并于第4、8、12和20周时，每组牺牲2只仓鼠进行分析。研究结果发现，摄取4、8、12周高脂饲料后，基因表现变化量达2倍以上的基因有51~328个，再以Ingenuity Pathway Analysis (IPA)生物路径分析相关基因表现后，发现有许多关于细胞凋亡、过氧化反应、发炎反应与细胞增生等相关基因表现的生物路径相较于控制组有较高程度的诱发。在第20周，高脂组仍然可以发现脂质生成作用的相关基因表现与DNA甲基化及转录抑制讯息传导基因。同时，肠道上皮细胞亦启动了多项关于伤害修复的调控机制，例如：glutathione-mediated detoxification，nucleotide excision repair。本实验证实在停止高脂喂食后，基因表现与长期高脂喂食的非常类似，但同时伴随修补基因进行损伤修复。

Abstract: Next-generation sequencing and big data analysis were used to investigate the high-fat diet on gene expression level of intestinal tissues in hamster. Sixteen hamsters were assigned to the control group and the high-fat group, respectively. At week 12, the high-fat group was switched from high-fat to the con-trol diet. At weeks 4, 8, 12, and 20, two hamsters from each group were sacrificed for analysis. The results showed that 51~328 genes exhibited more than a twofold change in expression level in high-fat diet group at week 4, 8, 12. Subsequently, Ingenuity Pathway Analysis (IPA) was used to analyze the relative gene expression levels. We found that significantly increased expression levels of genes associated with cell apoptosis, oxidative stress, inflammation, and cell proliferation compared to the control group. At week 20, the high-fat group still exhibited gene expressions related to lipid biosynthesis, DNA methylation, and transcriptional repression signaling, but concurrently, several regulatory mechanisms for damage repair were activated in intestinal epithelial cells, including Glutathione-mediated detoxification and nucleotide excision repair. This study demonstrated that the gene expressions at stopping the intake of high fat diet were similar to those of long-term high-fat feeding, but it was accompanied with upregulation of repair genes.