Background: The nuclear hormone receptor, Farnesoid X Receptor (FXR) regulates the
transcription of genes associated with bile acid metabolism and disposition.
Objective: This study investigates possible changes in the expression of target genes responsible for
amino acid conjugation, i.e., Bile Acid-CoA Synthetase (BACS) and bile acid-CoA: amino acid Nacetyltransferase
(BAT). These genes have been shown to be inducible by FXR agonists in rat models,
however, to date no studies have been conducted in a human hepatocyte model.
Results: In human hepatocytes, treatment with the FXR agonists GW4064 (1.0 µM) and WAY362450
(0.1 µM) did not significantly induce the mRNA expression of BACS and BAT genes. However, other
target genes associated with FXR activation, such as Bile Salt Export Pump (BSEP), Short Heterodimer
Partner (SHP), Multidrug Resistance-associated Protein 2 (MRP2) and Multidrug Resistance Protein
3 (MDR3), were upregulated. Interestingly, a follow up study conducted in rat hepatocytes indicated
that GW4064 induced the BACS gene while WAY362450 induced the BAT gene, confirming
literature results that these genes can be induced in rat.
Conclusion: In conclusion, there appears to be some species differences in the activation of FXR target