HNF4α--role in drug metabolism and potential drug target?

Curr Opin Pharmacol. 2010 Dec;10(6):698-705. doi: 10.1016/j.coph.2010.08.010.


Hepatocyte nuclear factor 4α (HNF4α) is a highly conserved member of the nuclear receptor superfamily of ligand-dependent transcription factors. It is best known as a master regulator of liver-specific gene expression, especially those genes involved in lipid transport and glucose metabolism. However, there is also a growing body of work that indicates the importance of HNF4α in the regulation of genes involved in xenobiotic and drug metabolism. A recent study identifying the essential fatty acid linoleic acid (LA, C18:2) as the endogenous, reversible ligand for HNF4α suggests that HNF4α may also be a potential drug target and that its activity may be regulated by diet. This review will discuss the role of HNF4α in drug metabolism, including the genes it regulates, the factors that regulate its activity, and its potential as a drug target.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cytochrome P-450 Enzyme System / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Female
  • Gene Expression
  • Gene Expression Regulation*
  • Hepatocyte Nuclear Factor 4 / genetics
  • Hepatocyte Nuclear Factor 4 / metabolism*
  • Humans
  • Inactivation, Metabolic*
  • Liver / metabolism
  • Male
  • Molecular Targeted Therapy
  • Pharmaceutical Preparations / metabolism*
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Regulatory Elements, Transcriptional
  • Sex Characteristics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • DNA-Binding Proteins
  • HNF4A protein, human
  • Hepatocyte Nuclear Factor 4
  • Pharmaceutical Preparations
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • Cytochrome P-450 Enzyme System