Diurnal variations of mouse plasma and hepatic bile acid concentrations as well as expression of biosynthetic enzymes and transporters

PLoS One. 2011 Feb 8;6(2):e16683. doi: 10.1371/journal.pone.0016683.


Background: Diurnal fluctuation of bile acid (BA) concentrations in the enterohepatic system of mammals has been known for a long time. Recently, BAs have been recognized as signaling molecules beyond their well-established roles in dietary lipid absorption and cholesterol homeostasis.

Methods and results: The current study depicted diurnal variations of individual BAs detected by ultra-performance liquid chromatography/mass spectrometry (UPLC/MS) in serum and livers collected from C57BL/6 mice fed a regular chow or a chow containing cholestyramine (resin). Circadian rhythms of mRNA of vital BA-related nuclear receptors, enzymes, and transporters in livers and ilea were determined in control- and resin-fed mice, as well as in farnesoid X receptor (FXR) null mice. The circadian profiles of BAs showed enhanced bacterial dehydroxylation during the fasting phase and efficient hepatic reconjugation of BAs in the fed phase. The resin removed more than 90% of BAs with β-hydroxy groups, such as muricholic acids and ursodeoxycholic acid, from serum and livers, but did not exert as significant influence on CA and CDCA in both compartments. Both resin-fed and FXR-null mouse models indicate that BAs regulate their own biosynthesis through the FXR-regulated ileal fibroblast growth factor 15. BA flux also influences the daily mRNA levels of multiple BA transporters.

Conclusion: BA concentration and composition exhibit circadian variations in mouse liver and serum, which influences the circadian rhythms of BA metabolizing genes in liver and ileum. The diurnal variations of BAs appear to serve as a signal that coordinates daily nutrient metabolism in mammals.

Publication types

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

MeSH terms

  • Animals
  • Bile Acids and Salts / biosynthesis
  • Bile Acids and Salts / blood*
  • Bile Acids and Salts / metabolism*
  • Carrier Proteins / genetics*
  • Cholestyramine Resin / pharmacology
  • Circadian Rhythm* / drug effects
  • Enterohepatic Circulation / drug effects
  • Gene Deletion
  • Gene Expression Regulation, Enzymologic* / drug effects
  • Liver / drug effects
  • Liver / enzymology
  • Liver / metabolism*
  • Liver / physiology
  • Male
  • Membrane Glycoproteins / genetics*
  • Mice
  • Mice, Inbred C57BL
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Cytoplasmic and Nuclear / deficiency
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Signal Transduction / drug effects
  • Transcriptome / drug effects


  • Bile Acids and Salts
  • Carrier Proteins
  • Membrane Glycoproteins
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • bile acid binding proteins
  • farnesoid X-activated receptor
  • Cholestyramine Resin