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Published on: March 11, 2017

Targeting farnesoid X receptor for liver and metabolic disorders

Stefano Fiorucci1, Gianni Rizzo, Annibale Donini

  • 1Dipartimento di Medicina Clinica e Sperimentale, University of Perugia, Perugia, Italy. fiorucci@unipg.it

Trends in Molecular Medicine
|June 26, 2007
PubMed

Insights

Farnesoid X receptor (FXR) regulates bile acid and cholesterol balance. Selective FXR modulators and combination therapies show promise for metabolic and liver disorders like NASH.

Area of Science:

  • Metabolic regulation and nuclear receptor signaling.

Background:

  • Farnesoid X receptor (FXR) is a nuclear receptor crucial for maintaining cholesterol and bile acid (BA) homeostasis.
  • FXR regulates genes involved in BA synthesis, uptake, and excretion in the liver, intestine, kidney, and adipose tissue.

Purpose of the Study:

  • To explore the therapeutic potential of FXR ligands for cholestasis, dyslipidemia, insulin resistance, and non-alcoholic steatohepatitis (NASH).
  • To address the challenge of off-target effects from broad FXR activation by developing selective FXR modulators.
  • To investigate combination therapies involving FXR and other nuclear receptors for liver and metabolic disorders.

Main Methods:

  • Review of current research on FXR function and therapeutic applications.
  • Analysis of FXR's role in metabolic pathways and its interaction with other nuclear receptors.

Main Results:

  • FXR activation impacts numerous genes, necessitating the development of pathway-selective modulators to minimize side effects.
  • FXR ligands are in clinical trials for various metabolic and liver conditions.
  • Interactions between FXR, constitutive androstane receptor, and pregnane X receptor suggest potential for combination therapies.

Conclusions:

  • Selective FXR modulators are key to mitigating side effects and enhancing therapeutic efficacy.
  • Combination therapies targeting FXR and other xenobiotic sensors offer a promising strategy for treating complex liver and metabolic diseases.

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