BA and fibroblast growth factor 19 (FGF19) levels (a surrogate for intestinal farnesoid X receptor [FXR] activity), patatin-like phospholipase domain-containing 3 (PNPLA3) and transmembrane 6 superfamily member 2 (TM6SF2) variants, and gut microbiota profiles in lean and non-lean NAFLD were investigated in a cohort of Caucasian patients with biopsy-proven NAFLD (n = 538), lean healthy controls (n = 30), and experimental murine models.
Early evidence has suggested the potential of bile acid receptor agonists in NAFLD management, but their long-term safety and effectiveness need further clarification.
Some new pharmacological strategies act broadly to alter energy balance or influence pathways that contribute to NAFLD (e.g., agonists for PPAR γ, PPAR α/δ, FXR and analogs for FGF-21, and GLP-1).
Noteworthy, experiments with primary hepatocytes from male and female mice show that they express Takeda G protein-coupled bile acid receptor and that it and bile acid enterohepatic circulation might be accountable for sex dimorphism in nonalcoholic fatty liver disease development.
These findings indicate that the Nrf2/FXR/LXRα pathway might synergistically regulate both endogenous and exogenous metabolism in NAFLD mice and LXRα may be a novel therapeutic target of curcumin for the prevention and treatment of NAFLD.
For its role as guardian of metabolism, FXR has been identified a promising pharmacological target in liver bile acid and lipid accumulation, such as cholestasis and non-alcoholic fatty liver disease (NAFLD).
The bile acid receptorFXR may be a promising novel therapeutic target for the treatment of NAFLD/NASH, fibrosis and portal hypertension, but the prognostic implications of associated changes in low- and high-density lipoprotein cholesterol require further studies.