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Related Experiment Video

Updated: May 10, 2026

Using Multi-fluorinated Bile Acids and In Vivo Magnetic Resonance Imaging to Measure Bile Acid Transport
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Single and Multiple Doses of Seladelpar Decrease Diurnal Markers of Bile Acid Synthesis in Mice.

Edward E Cable1, Jeffrey W Stebbins1, Jeff D Johnson1

  • 1CymaBay Therapeutics Inc., Fremont, California, USA.

PPAR Research
|April 14, 2025
PubMed
Summary

Seladelpar, a PPARδ agonist, reduces bile acid synthesis by increasing FGF21 and altering gene expression in mice. This PPAR agonist shows therapeutic potential for cholestatic diseases.

Keywords:
PPARPPAR deltabile metabolismcircadian rhythmseladelpar

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Area of Science:

  • Pharmacology
  • Hepatology
  • Molecular Biology

Background:

  • Peroxisome proliferator-activated receptors (PPARs) are key regulators of bile acid metabolism.
  • PPAR agonists are potential therapeutics for cholestatic liver diseases.
  • Understanding seladelpar's effects on bile acid biosynthesis and gene expression is crucial.

Purpose of the Study:

  • To investigate the effects of single and multiple doses of seladelpar, a PPARδ agonist, on bile acid metabolism and gene expression in mice.
  • To assess seladelpar's impact on plasma C4 (bile acid biosynthesis proxy) and Fibroblast Growth Factor 21 (Fgf21) levels.
  • To analyze liver gene expression changes induced by seladelpar treatment.

Main Methods:

  • Male and female C57BL/6 mice were administered seladelpar (10 mg/kg/day) or vehicle via oral gavage.
  • Plasma C4 and Fgf21 levels were measured at various time points post-dosing.
  • Liver gene expression was analyzed using untargeted RNA sequencing.

Main Results:

  • Seladelpar significantly reduced plasma C4 and increased plasma Fgf21 levels in both male and female mice.
  • Treatment decreased cholesterol 7α-hydroxylase mRNA and increased Fgf21 mRNA in the liver.
  • RNA sequencing revealed upregulation of PPAR-responsive genes and a strong correlation between single and multiple dose effects.

Conclusions:

  • Seladelpar treatment effectively reduces bile acid synthesis in mice.
  • The mechanism involves upregulation of Fgf21 and modulation of other PPAR-responsive genes.
  • These findings support seladelpar's potential as a therapeutic agent for cholestatic diseases.