System Analysis of The Functional Cross-Talk Between PPARα, LXR and FXR in HepaRG Liver Cells

The purpose of the present study was to explore in liver cells the connectivity that operates between three nuclear receptors in the liver, LXR, FXR, and PPARa, all three known to act on lipid and glucose metabolism, and also on inflammation. The human cell line HepaRG was selected for its proximity to human primary hepatocytes. Global gene expression of differentiated HepaRG cells was assessed after 4 hours and 24 hours of exposure to GW3965 (LXR agonist), GW7647 (PPARα agonist), and GW4064 and CDCA (FXR synthetic and natural agonist, respectively). The study includes 36 samples from two time points, 4h and 24h. The two time points were analyzed separately. The cell cultures received six different treatments: four ligands binding to nuclear receptors (CDCA, FXR-L, LXR-L and PPARα-L) and two control treatments (DMSO vehicle control and untreated control). There were three replicate cell cultures for each treatment. For the data analysis, DMSO and untreated control were lumped together into a single control group.