BACKGROUND Insulin resistance (IR) and lipid peroxidation are accepted as 'two-hit' hypothesis of Non-alcoholic fatty liver disease (NAFLD). However, there are few published research on identifying genes which connect lipid and glucose metabolism by gene microarray. OBJECTIVE To identify target genes related to lipid and glucose metabolism that might be responsible for the pathogenesis of NAFLD. METHODS A rat model of NAFLD was established by feeding male rats with high-fat diet and gene expression profiles of liver tissues were determined using Agilent DNA microarray. We then investigated differentially expressed genes (DEGs) and intersection of them by using Gene Ontology (GO) and Pathway Analyses. Target genes were verified by Real-time polymerase chain reaction (RT-PCR). RESULTS Compared with control, 932 genes, including 783 up-regulated and 149 down-regulated, exhibited differences in expression. The up-regulated genes were involved in biosynthesis, cell development, cell differentiation and down-regulated genes contributed to biological metabolic process, adipokine metabolic pathway and insulin signaling pathway. We identified genes involved in insulin signaling pathway, Notch signaling pathway and lipid synthetic process to be closely related to liver fat accumulation and insulin resistance. Among them, IGFBP7, Notch1 and HMGCR were up-regulated (2.85-fold, 3.22-fold, and 2.06-fold, respectively, all P < 0.05) and ACACB was down-regulated (2.08-fold, P < 0.01). These four genes supposed to connect lipid and glucose metabolism after GO and Pathway analyses. CONCLUSIONS These findings provide innovative information on the whole genome expression profile due to high-fat diet feeding, and bring new insight into the regulating effects of genes on the lipid and glucose metabolism of NAFLD.

中文翻译：

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非酒精性脂肪肝疾病中与脂质和葡萄糖代谢相关的靶基因。

背景技术胰岛素抵抗（IR）和脂质过氧化被认为是非酒精性脂肪肝疾病（NAFLD）的“两次打击”假设。然而，关于通过基因芯片鉴定连接脂质和葡萄糖代谢的基因的研究很少。目的确定与脂质和葡萄糖代谢有关的靶基因，这些靶基因可能与NAFLD的发病机理有关。方法采用高脂饮食喂养雄性大鼠，建立NAFLD大鼠模型，并使用安捷伦DNA微阵列技术测定肝组织的基因表达谱。然后，我们通过使用基因本体论（GO）和路径分析来研究差异表达基因（DEG）及其交叉。通过实时聚合酶链反应（RT-PCR）验证靶基因。结果与对照组相比，有932个基因，包括783个上调和149个下调，表现出表达差异。上调的基因参与生物合成，细胞发育，细胞分化，而下调的基因参与生物代谢过程，脂肪因子代谢途径和胰岛素信号传导途径。我们发现参与胰岛素信号通路，Notch信号通路和脂质合成过程的基因与肝脂肪积累和胰岛素抵抗密切相关。其中，IGFBP7，Notch1和HMGCR被上调（分别为2.85倍，3.22倍和2.06倍，所有P <0.05），而ACACB被下调（2.08倍，P <0.01）。在GO和Pathway分析后，这四个基因被认为与脂质和葡萄糖的代谢有关。