FXR isoform selective effects on hepatoma cell line HepG2

The farnesoid X receptor (FXR) is a nuclear receptor activated by bile acids that regulates bile acid metabolism, glucose and cholesterol homeostasis. FXR is expressed as four isoforms (a1-4), and their relative abundance is tissue specific. Human livers express predominantly FXR isoforms a1 and a2. From mouse studies we know that the FXR agonist obeticholic acid (OCA) regulates expression of many genes in the liver. However, there is currently no data on the effects of OCA on FXR isoform selective gene regulation. This is particularly relevant since the relative FXR isoform amounts in the liver are regulated by general bioenergetic cues (Correia JC et al. 2015). In this study we investigate the effect of variations in FXR isoforms a1 or a2 expression on HepG2 cell lines response to treatment with OCA. Overall design: HepG2 cells were transduced with FXR isoforms a1 or a2, or GFP using lentiviral vectors (pLV IRES PuroR). After selection, the cells were treated with the FXR agonist Obeticholic acid for 8 hours before lysis. RNA was extracted and prepared for sequencing analysis.