Screening of Genes Related to Glucose and Lipid Metabolism in Non-alcoholic Fatty Liver Disease by Gene Microarray

We used gene expression microarray to explore the correlation between gene expression profiles and find out the target genes related to lipid and glucose metabolism in NAFLD. A rat model of NAFLD was established by feeding male rats with high-fat diet and Agilent DNA microarray was used to detect gene expression profiles of liver tissues. We explored differentially expressed genes and intersection of them by using Gene ontology (GO) and Pathway analyses. Then, target genes were verified by Real-time polymerase chain reaction (RT-PCR). There were 932 genes, including 783 up-regulated and 149 down-regulated, differed in expression compared to those of control rats. The up-regulated genes were involved in biosynthesis, cell development, cell differentiation and down-regulated genes mainly contributed to biological metabolic process and stress reaction. We identified genes involved in insulin signaling pathway, Notch signaling pathway, adipocytokin and linoleic acid metabolism to be closely related to liver fat content and insulin resistance. Among them, genes which supposed to connect glucose and lipid metabolism were screened (IGFBP7, Notch1, HMGCR and ACACB) and then validated by real-time PCR. These data provide innovative information on the whole genome expression profile due to high-fat diet feeding and bring important insights into the mechanism of NAFLD.本研究采用基因表达微阵列技术探究基因表达谱的相关性，筛选非酒精性脂肪性肝病（NAFLD）中与脂糖代谢相关的靶基因。通过高脂饮食饲喂雄性大鼠构建NAFLD大鼠模型，并采用安捷伦（Agilent）DNA微阵列检测肝脏组织的基因表达谱。通过基因本体（Gene Ontology, GO）富集分析与通路富集分析，筛选差异表达基因并获取其交集基因；随后采用实时荧光定量聚合酶链式反应（Real-time polymerase chain reaction, RT-PCR）对靶基因进行验证。与对照组大鼠相比，本研究共筛选得到932个差异表达基因，其中上调基因783个、下调基因149个。上调基因参与生物合成、细胞发育与细胞分化等生物学过程，下调基因则主要参与生物代谢过程及应激反应。本研究发现，参与胰岛素信号通路、Notch信号通路、脂肪细胞因子及亚油酸代谢的基因与肝脏脂肪含量及胰岛素抵抗密切相关。其中，本研究筛选出与糖脂代谢相关的核心基因（IGFBP7、Notch1、HMGCR及ACACB），并通过实时荧光定量PCR完成验证。本研究所得数据为高脂饮食诱导下的全基因组表达谱提供了创新性研究视角，同时为阐明NAFLD的发病机制提供了重要参考。