Nuclear bile acid receptor FXR as pharmacological target: Are we there yet?

Abstract 

The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily that is primarily expressed in the enterohepatic system where it functions as intracellular sensor for bile acids. Ligand dependent FXR activation induces transcriptional responses to coordinately regulate bile acid, cholesterol, triglyceride and glucose metabolism, and to protect the intestinal mucosa from bacterial overgrowth and inflammatory insults. Here we discuss the latest discoveries in FXR-driven metabolic pathways with relevance to pathophysiology and novel therapeutic approaches of several conditions such as hypertriglyceridemia, type 2 diabetes, cholesterol gallstone disease, steato-hepatitis and metabolic syndrome.

Abbreviations: ABC, ATP binding cassette transporter, ASBT, apical sodium dependent bile acid transporter, BSEP, bile salt export pump, CA, cholic acid, CDCA, chenodeoxycholic acid, CGD, cholesterol gallstone disease, CYP7A1, cholesterol 7α-hydroxylase, DCA, deoxycholic acid, FBP1, fructose 1,6-bis phosphatase, FXR, farnesoid X receptor, G6Pase, glucose-6-phosphatase, GR, glucocorticoid receptor, HDL, high density lipoprotein, HNF-4, hepatocyte nuclear factor 4, LCA, litocholic acid, LDL, low density lipoprotein, LXR, liver X receptor, MDR, multi-drug resistance, NR, nuclear receptors, NTCP, sodium taurocholate cotransporting polypeptide, OST, organic solute transporter, PEPCK, phosphoenolpyruvate carboxykinase, PGC1α, PPARγ coactivator 1α, PPAR, peroxisome proliferators-activated receptor, SHP, small heterodimer partner, SREBP-1c, sterol regulatory element-binding protein-1c, SRB1, scavenger receptor B1, TG, triglycerides, VLDL, very low density lipoprotein

Keywords: Cholesterol, Farnesoid X receptor, Gallstones, Hypertriglyceridemia, Metabolic syndrome