Animal models to study bile acid metabolism

Biochim Biophys Acta Mol Basis Dis. 2019 May 1;1865(5):895-911. doi: 10.1016/j.bbadis.2018.05.011. Epub 2018 May 18.

Abstract

The use of animal models, particularly genetically modified mice, continues to play a critical role in studying the relationship between bile acid metabolism and human liver disease. Over the past 20 years, these studies have been instrumental in elucidating the major pathways responsible for bile acid biosynthesis and enterohepatic cycling, and the molecular mechanisms regulating those pathways. This work also revealed bile acid differences between species, particularly in the composition, physicochemical properties, and signaling potential of the bile acid pool. These species differences may limit the ability to translate findings regarding bile acid-related disease processes from mice to humans. In this review, we focus primarily on mouse models and also briefly discuss dietary or surgical models commonly used to study the basic mechanisms underlying bile acid metabolism. Important phenotypic species differences in bile acid metabolism between mice and humans are highlighted.

Keywords: Enterohepatic circulation; Enzyme; Intestine; Liver; Mouse model; Transporter.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Bile Acids and Salts / biosynthesis*
  • Bile Acids and Salts / genetics
  • Bile Acids and Salts / metabolism
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cytochrome P-450 Enzyme System / genetics*
  • Cytochrome P-450 Enzyme System / metabolism
  • Humans
  • Liver / blood supply
  • Liver / metabolism*
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / metabolism

Substances

  • Bile Acids and Salts
  • Carrier Proteins
  • Membrane Glycoproteins
  • bile acid binding proteins
  • Cytochrome P-450 Enzyme System