These data provide useful information on the global gene expression changes due to high-fat emulsion feeding and bring important insights into the mechanisms of NAFLD.

After partial hepatectomy (PH), the recovery of liver mass is mainly mediated by proliferation and enlargement of hepatocytes. Therefore, measuring the transcriptional profiling of hepatocytes after PH will be helpful in exploring the mechanism of liver regeneration (LR). Firstly, hepatocytes were isolated from rat regenerating liver at different time points following PH, and then global gene expression analysis of hepatocytes was performed using Rat Genome 230 2.0 Array. The results demonstrated that 1,417 genes in the array (including 767 known genes) were identified to be LR-related. Clustering analysis demonstrated that 767 known genes fell into six classes with distinct expression kinetics. When gene expression patterns were combined with gene functions, genes involved in acute-phase response and defense response were rapidly elevated in early phases; those in cell proliferation and DNA replication were significantly up-expressed in middle phase; a growing number of cell adhesion-involved genes were up-regulated as regeneration progressed; those in amino acid and lipid metabolism showed persistent down-regulation during LR. Based on the above analyses, it was suggested that hepatocyte defense mechanism was quickly triggered after PH; cell proliferation became active in middle phase; cell adhesion was strengthened in late phase; amino acid and lipid metabolism were attenuated during LR. Additionally, comparative analysis between transcriptional profiling of hepatocytes and regenerating liver indicated a major contribution of hepatocytes to LR.

Liver regeneration (LR) after partial hepatectomy (PH) requires the coordinate contribution of different cell types. Liver sinusoidal endothelial cells (LSECs), representing the largest population of nonparenchymal cells, are proven to be crucial in LR. However, the details about their implications in regeneration are not still clear. In this study, percoll density centrifugation and immunomagentic bead methods were used to isolate LSECs with high purity and yield; global transcriptional profiles of LSECs during the regeneration were investigated by microarray. 1,629 genes were identified to be LR-related. Among them, there were 833 known genes whose expression patterns were clustered into eight classes. Gene function enrichment analysis showed that genes involved in the major LSEC functions, i.e., coagulation, phagocytosis, and transport, were highly enriched in cluster characterized by rapid induction and gradual return, suggesting the quick reestablishment of LSEC function after PH. Genes in immunity/inflammation and defense response were enriched in clusters exhibiting transient downregulation and quick recovery, possibly being associated with suppression of immunity/inflammation pathway in LSECs at early phase. Genes in glycogen synthesis and glycolysis were enriched in the clusters marked by "significant increase and gradual return" and "slight increase and then downregulation", implying an enhanced carbohydrate metabolism at early phase; detoxification-related genes were markedly distributed in the cluster with feature of rapid increase and then reduction, which was helpful in eliminating waste substance. Taken together, the measurement of gene expression profiling of LSECs and expression pattern analysis of functionally categorized genes gave insight into the mechanism of action of this cell on LR.

This study performed a large-scale, high-throughput analysis of transcriptional profiling of liver stellate cells (LSCs) at the cellular level to investigate changes in the biological activity of LSCs during rat liver regeneration (LR) and the relation of these changes to LR. First, a rat liver regeneration model was established by partial hepatectomy (PH). Stellate cells were isolated in high purity and yield from the regenerating rat liver by Percoll density gradient centrifugation and immunomagnetic bead sorting. The changes in gene expression of LSCs after PH were examined using a rat genome 230 2.0 array composed of 24622 genes. The results indicated that 10241 of the 24622 genes investigated on the array were differentially expressed in LSCs. Of the 10241 genes, 1563 known genes were related to LR, which were grouped into three major gene expression clusters according to three-fold cut-off threshold: the upregulated gene cluster, the down-regulated gene cluster, and the cluster composed of genes showing complex changes in expression. Additionally, the genes were grouped into those involved in transcription regulation, signal transduction, transport, cellular metabolism, inflammation and immunity by functional analysis. When gene expression profiles were combined with the results of gene functional analysis, most of the genes involved in cytokine secretion and retinol metabolism in LSCs were significantly enriched in the cluster characterized by decreased expression, whereas genes involved in lipid metabolism were mostly enriched in the cluster showing increased expression. Based on further analysis of genes expressed in a phase-dependent manner during LR, it was suggested that lipid metabolism in LSCs was enhanced in the whole regeneration process, and that immune response and cytokine secretion were impaired during all three regenerative phases.

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