Target genes associated with lipid and glucose metabolism in non-alcoholic fatty liver disease

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.