RNA sequencing in human HepG2 hepatocytes reveals PPAR-α mediates transcriptome responsiveness of bilirubin

Darren M. Gordon, Thomas M. Blomquist, Scott A. Miruzzi, Robert McCullumsmith, David E. Stec, Terry D. Hinds

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


Bilirubin is a potent antioxidant that reduces inflammation and the accumulation of fat. There have been reports of gene responses to bilirubin, which was mostly attributed to its antioxidant function. Using RNA sequencing, we found that biliverdin, which is rapidly reduced to bilirubin, induced transcriptome responses in human HepG2 hepatocytes in a peroxisome proliferator-activated receptor (PPAR)-α-dependent fashion (398 genes with >2-fold change; false discovery rate P < 0.05). For comparison, a much narrower set of genes demonstrated differential expression when PPAR-α was suppressed via lentiviral shRNA knockdown (23 genes). Gene set enrichment analysis revealed the bilirubin-PPAR-α transcriptome mediates pathways for oxidationreduction processes, mitochondrial function, response to nutrients, fatty acid oxidation, and lipid homeostasis. Together, these findings suggest that transcriptome responses from the generation of bilirubin are mostly PPAR-α dependent, and its antioxidant function regulates a smaller set of genes.

Original languageEnglish
Pages (from-to)234-240
Number of pages7
JournalPhysiological Genomics
Issue number6
StatePublished - 2019

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health Grants K01HL-125445 (to T. D. Hinds) and P20GM-104357-02 (D. E. Stec).

Publisher Copyright:
© 2019 the American Physiological Society.


  • Gene
  • Liver
  • PPAR
  • Transcription

ASJC Scopus subject areas

  • Physiology
  • Genetics


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