FXR

2022-11-07:

FXR (Farsenoid X Receptor) (Bile Acid Receptor) #

• Ligands include bile acids/bile salts, cafestol, ivermectin.
• In the ileum: Induces FGF1515/19 -> CYP7A1 inhibition
• In the liver: Induces SHP, which I think has 2 ways of inhibiting CYP7A1.

• Activation in diabetic mice reduces plasma glucose and improves Insulin Sensitivity.
• Farnesoid X receptor: a master regulator of hepatic triglyceride and glucose homeostasis
  • Suppresses lipogenesis and activates PPAR-α to promote FAO.
    • Regulation of hepatic metabolic pathways by the orphan nuclear receptor SHP
      • SHP transgenic mice see liver steatosis due to indirect activation of PPAR-γ and SREBP-1c, and direct SHP-mediated direct repression of certain target genes, obviously such as inhibition of CYP7A1.
        • The lack of recruitment of SHP to the SREBP-1c, CD36 and FAS promoters points to an indirect effect
      • In terms of lipogenesis: mRNA of FASN, acetyl-coA carboxylase, stearoyl-coa reductase, ACL, and CD36 increased.
      • In terms of transcription factors: We did not observe significant differences between wild-type and SHP-Tg mice in the expression of LRH-1, HNF-4α, LXRα, HNF-1α, CAR, PXR, RXRα and PPARα