ABSTRACT
<p><b>OBJECTIVES</b>To explore the changes of hepatic gene expression during the course of nonalcoholic fatty liver disease (NAFLD) development in rats.</p><p><b>METHODS</b>A rat model of NAFLD was developed by feeding the animals a high-fat diet for 24 weeks. Liver tissues of the model rats and the control rats were analyzed at different time points using rat U230A (Affymetrix GeneChip), which covers 15650 genes.</p><p><b>RESULTS</b>Compared with the control rats, the number of genes expressed differently in the model group rats at 4 and 8 weeks was 426 and 540. The up-regulated genes among them were intracellular phosphorylase genes, metabolic enzyme genes, fatty acid binding protein genes, cytochrome P450 genes, cellular transcription and differentiation genes. The down-regulated genes were ionic channel genes, hormone receptor genes, and cytoskeleton genes. At the 12th week, the number of the genes expressed differently was 501, in which 352 were up-regulated genes, including genes related to inflammation and apoptosis such as interleukin and Toll-like receptor 4. At the 16th week, the number of the differently expressed genes was 665, with 430 up-regulated, such as those related to the inflammation and apoptosis genes and collagen I and fibrosis genes, however cell regeneration genes were down-regulated. At the 24th week the number was 663, of which fibroblast growth factor, transforming growth factor and insulin-like growth factor genes were up-regulated. Of all the differently expressed genes, the number of up-regulated genes was 128, including 10 lipogenic genes, 46 metabolic genes, 15 inflammation genes, 10 apoptosis genes, and 16 fibrosis genes; and the down-regulated genes were 52, including 6 hormone receptor genes, 5 cell regeneration genes and 11 electron transport genes.</p><p><b>CONCLUSION</b>The changes of the hepatic gene expression of rats fed a fat-rich diet are related to the duration of the feeding, and are correlated with their histopathology in the livers.</p>