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PPARα: A potential therapeutic target of cholestasis

Xiaoyin Ye1, Tong Zhang1, Han Han2

  • 1School of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Frontiers in Pharmacology
|August 4, 2022
PubMed

Insights

Peroxisome proliferator-activated receptor alpha (PPARα) agonists show promise in treating cholestasis by regulating bile acid metabolism and reducing liver inflammation. This offers a new therapeutic avenue beyond existing farnesoid X receptor (FXR) activators.

Area of Science:

  • Hepatology and Gastroenterology
  • Molecular Biology and Pharmacology

Background:

  • Bile acid accumulation in the liver causes cholestasis and hepatocyte injury.
  • Nuclear receptors, including farnesoid X receptor (FXR), regulate bile acid homeostasis.
  • Current FXR agonists (UDCA, OCA) have limitations due to patient unresponsiveness and side effects like pruritus.

Purpose of the Study:

  • To explore the role of peroxisome proliferator-activated receptor alpha (PPARα) in bile acid transport and metabolism.
  • To investigate the anti-inflammatory effects of PPARα in cholestatic liver injury.
  • To discuss the therapeutic potential of PPARα agonists for cholestatic liver disorders.

Main Methods:

  • Review of existing literature on PPARα function in bile acid regulation.
  • Analysis of PPARα's anti-inflammatory mechanisms.
  • Discussion of clinical applications of PPARα agonists in cholestasis.

Main Results:

  • PPARα activation influences bile acid synthesis and transport.
  • PPARα exhibits significant anti-inflammatory properties beneficial for liver injury.
  • PPARα agonists represent a novel therapeutic strategy for cholestatic conditions.

Conclusions:

  • PPARα plays a crucial role in managing bile acid metabolism and mitigating liver damage.
  • PPARα agonists offer a promising alternative or adjunct therapy for cholestasis, potentially overcoming limitations of FXR-targeted drugs.
  • Further research into PPARα agonists is warranted for effective treatment of cholestatic liver diseases.
Keywords:
cholestasisinflammationliver injuryperoxisome proliferator-activated receptor alphatherapeutic target

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