Impact of fatty acids on human UDP-glucuronosyltransferase 1A1 activity and its expression in neonatal hyperbilirubinemia

Sci Rep. 2013 Oct 9;3:2903. doi: 10.1038/srep02903.

Abstract

While breast milk has been known as a cause of neonatal hyperbilirubinemia, the underlying mechanism of breast milk-induced jaundice has not been clarified. Here, the impact of fatty acids on human UDP-glucuronosyltransferase (UGT) 1A1--the sole enzyme that can metabolize bilirubin--were examined. Oleic acid, linoleic acid, and docosahexaenoic acid (DHA) strongly inhibited UGT1A1 activity. Forty-eight hours after a treatment with a lower concentration of DHA (10 mg/kg), total bilirubin significantly increased in neonatal hUGT1 mice, which are human neonatal jaundice models. In contrast, treatments with higher concentrations of fatty acids (0.1-10 g/kg) resulted in a decrease in serum bilirubin in hUGT1 mice. It was further demonstrated that the treatment with higher concentrations of fatty acids induced UGT1A1, possibly by activation of peroxisome proliferator-activated receptors. Our data indicates that activation of peroxisome proliferator-activated receptors would increase UGT1A1 expression, resulting in reduction of serum bilirubin levels in human infants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Bilirubin / metabolism*
  • Chromatography, High Pressure Liquid
  • Docosahexaenoic Acids / pharmacology*
  • Glucuronosyltransferase / genetics
  • Glucuronosyltransferase / metabolism*
  • Humans
  • Hyperbilirubinemia, Neonatal / drug therapy
  • Hyperbilirubinemia, Neonatal / enzymology*
  • Hyperbilirubinemia, Neonatal / genetics
  • Jaundice, Neonatal / drug therapy
  • Jaundice, Neonatal / enzymology*
  • Jaundice, Neonatal / genetics
  • Linoleic Acids / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Oleic Acids / pharmacology*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Linoleic Acids
  • Oleic Acids
  • RNA, Messenger
  • Docosahexaenoic Acids
  • UGT1A1 enzyme
  • Glucuronosyltransferase
  • Bilirubin