Peroxisome proliferator-activated receptor-β/δ protects against chemically induced liver toxicity in mice

Weiwei Shan, Christopher J. Nicol, Shinji Ito, Moses T. Bility, Mary J. Kennett, Jerrold M. Ward, Frank J. Gonzalez, Jeffrey M. Peters

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Abstract

Potential functional roles for the peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) in skeletal muscle fatty acid catabolism and epithelial carcinogenesis have recently been described. Whereas PPARβ/δ is expressed in liver, its function in this tissue is less clear. To determine the role of PPARβ/δ in chemically induced liver toxicity, wild-type and PPARβ/δ-null mice were treated with azoxymethane (AOM) and markers of liver toxicity examined. Bile duct hyperplasia, regenerative hyperplasia, and increased serum alanine aminotransferase (ALT) were found in AOM-treated PPARβ/δ-null mice, and these effects were not observed in similarly treated wild-type mice. Exacerbated carbon tetrachloride (CCl4) hepatoxicity was also observed in PPARβ/δ-null as compared with wild-type mice. No differences in messenger RNAs (mRNAs) encoding cytochrome2E1 required for the metabolic activation of AOM and CCl4 were observed between wild-type or PPARβ/δ-null mice in response to CCl4. Significant differences in the expression of genes reflecting enhanced nuclear factor kappa B (NF-κB) activity were noted in PPARβ/δ-null mice. Conclusion: Results from these studies show that PPARβ/δ is protective against liver toxicity induced by AOM and CCl4, suggesting that this receptor is hepatoprotective against environmental chemicals that are metabolized in this tissue.

Original languageEnglish (US)
Pages (from-to)225-235
Number of pages11
JournalHepatology
Volume47
Issue number1
DOIs
StatePublished - Jan 1 2008

All Science Journal Classification (ASJC) codes

  • Hepatology

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    Shan, W., Nicol, C. J., Ito, S., Bility, M. T., Kennett, M. J., Ward, J. M., Gonzalez, F. J., & Peters, J. M. (2008). Peroxisome proliferator-activated receptor-β/δ protects against chemically induced liver toxicity in mice. Hepatology, 47(1), 225-235. https://doi.org/10.1002/hep.21925