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[FXR modulators and cholestatic diseases.]

Domenico Alvaro1, Maria Consiglia Bragazzi1, Rosanna Venere1

  • 1Dipartimento di Medicina Traslazionale e di Precisione, Sapienza Università di Roma.

Recenti Progressi in Medicina
|February 24, 2021
PubMed

Insights

Farnesoid X receptor (FXR) activation regulates bile acid metabolism, inflammation, and fibrosis. FXR agonists show promise for treating cholestatic liver diseases like primary biliary cholangitis and cholangiocarcinoma.

Area of Science:

  • Hepatology
  • Nuclear Receptors
  • Pharmacology

Background:

  • The Farnesoid X nuclear receptor (FXR) is a bile acid-activated nuclear receptor.
  • FXR plays a critical role in regulating bile acid homeostasis, lipid, and carbohydrate metabolism.
  • FXR activation also exhibits anti-inflammatory and antifibrotic properties.

Purpose of the Study:

  • To review the role of FXR in liver pathologies.
  • To discuss the therapeutic potential of FXR agonists in cholestatic liver diseases.

Main Methods:

  • Literature review of FXR research over the past decade.
  • Analysis of studies investigating FXR agonists in preclinical and clinical settings.

Main Results:

  • FXR activation suppresses bile acid synthesis and promotes excretion.
  • FXR influences over 250 genes involved in metabolism, inflammation, and fibrosis.
  • Synthesized FXR agonists have demonstrated therapeutic benefits in cholestatic diseases.

Conclusions:

  • FXR is a key regulator of liver function and disease.
  • FXR agonists represent a promising therapeutic strategy for cholestatic liver diseases, including primary biliary cholangitis, primary sclerosing cholangitis, and cholangiocarcinoma.

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