Effect of nine diets on xenobiotic transporters in livers of mice

Xenobiotica. 2015;45(7):634-41. doi: 10.3109/00498254.2014.1001009. Epub 2015 Jan 8.

Abstract

1. Lifestyle diseases are often caused by inappropriate nutrition habits and attempted to be treated by polypharmacotherapy. Therefore, it is important to determine whether differences in diet affect the disposition of drugs. Xenobiotic transporters in the liver are essential in drug disposition. 2. In the current study, mice were fed one of nine diets for 3 weeks. The mRNAs of 23 known xenobiotic transporters in livers of mice were quantified by microarray analysis, and validated by branched DNA assay. The mRNAs of 15 transporters were altered by at least one diet. Diet-restriction (10) and the atherogenic diet (10) altered the expression of the most number of transporters, followed by western diet (8), high-fat diet (4), lab chow (2), high-fructose diet (2) and EFA-deficient diet (2), whereas the low n-3 FA diet had no effect on these transporters. Seven of the 11 xenobiotic transporters in the Slc family, three of four in the Abcb family, two of four in the Abcc family and all three in the Abcg family were changed significantly. 3. This first comprehensive study indicates that xenobiotic transporters are altered by diet, and suggests there are likely diet-drug interactions due to changes in the expression of drug transporters.

Keywords: Disposition; drugs; mRNA expression; microarray.

Publication types

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

MeSH terms

  • Acetic Acid / metabolism
  • Animals
  • Bile Canaliculi / metabolism
  • Branched DNA Signal Amplification Assay
  • Cluster Analysis
  • Diet*
  • Gene Expression Profiling
  • Hepatocytes / metabolism
  • Liver / metabolism*
  • Male
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Mice, Inbred C57BL
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reproducibility of Results
  • Xenobiotics / metabolism*

Substances

  • Membrane Transport Proteins
  • RNA, Messenger
  • Xenobiotics
  • Acetic Acid