Effects of feeding bile acids and a bile acid sequestrant on hepatic bile acid composition in mice

Youcai Zhang; Curtis D. Klaassen

doi:10.1194/jlr.M007641

Effects of feeding bile acids and a bile acid sequestrant on hepatic bile acid composition in mice[S]

Youcai Zhang and
Curtis D. Klaassen¹

Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS

Abstract

An improved ultra performance liquid chromatography-tandem mass spectrometry (UPLC/MS/MS) method was established for the simultaneous analysis of various bile acids (BA) and applied to investigate liver BA content in C57BL/6 mice fed 1% cholic acid (CA), 0.3% deoxycholic acid (DCA), 0.3% chenodeoxycholic acid (CDCA), 0.3% lithocholic acid (LCA), 3% ursodeoxycholic acid (UDCA), or 2% cholestyramine (resin). Results indicate that mice have a remarkable ability to maintain liver BA concentrations. The BA profiles in mouse livers were similar between CA and DCA feedings, as well as between CDCA and LCA feedings. The mRNA expression of Cytochrome P450 7a1 (Cyp7a1) was suppressed by all BA feedings, whereas Cyp7b1 was suppressed only by CA and UDCA feedings. Gender differences in liver BA composition were observed after feeding CA, DCA, CDCA, and LCA, but they were not prominent after feeding UDCA. Sulfation of CA and CDCA was found at the 7-OH position, and it was increased by feeding CA or CDCA more in male than female mice. In contrast, sulfation of LCA and taurolithocholic acid (TLCA) was female-predominant, and it was increased by feeding UDCA and LCA. In summary, the present systematic study on BA metabolism in mice will aid in interpreting BA-mediated gene regulation and hepatotoxicity.

Footnotes

↵1 To whom correspondence should be addressed. e-mail: cklaasse{at}kumc.edu
Abbreviations:

alloLCA, allolithocholic acid

3α-hydroxy-5α–cholan-24-oic acid

BA

bile acid

BAG

bile acid glucuronide

BAS

bile acid sulfate

CA, cholic acid

3α,7α,12α–trihydroxy-5β–cholan-24-oic acid

CA3S

cholic acid 3-sulfate

CA7S

cholic acid 7-sulfate

CA12S

cholic acid 12-sulfate

Cyp

cytochrome P450

CDCA, chenodeoxycholic acid

3α,7α-dihydroxy-5β–cholan-24-oic acid

CDCA3S

chenodeoxycholic acid 3-sulfate

CDCA7S

chenodeoxycholic acid 7-sulfate

DCA, deoxycholic acid

3α,12α-dihydroxy-5β–cholan-24-oic acid

3-DCA, 3-deoxycholic acid

7α,12α-dihydroxy-5β–cholan-24-oic acid

DCA3S

deoxycholic acid 3-sulfate

DCA12S

deoxycholic acid 12-sulfate

3-dehydroCA

7α,12α-dihydroxy-3-oxo-5β–cholan-24-oic acid

3-dehydroCDCA

7α-dihydroxy-3-oxo-5β–cholan-24-oic acid

dehydroLCA

3-oxo-5β-cholan-24-oic acid

Gapdh

Glyceraldehyde-3-phosphate dehydrogenase

GCA, glycocholic acid

3α,7α,12α–trihydroxy-5β–cholan-24-oylglycine

GCDCA, glycochenodeoxycholic acid

3α,7α-dihydroxy-5β–cholan-24-oylglycine

GCDCA3S

glycochenodeoxycholic acid 3-sulfate

GDCA, glycodeoxycholic acid

3α,12α-dihydroxy-5β–cholan-24-oylglycine

GDCA3S

glycodeoxycholic acid 3-sulfate

GHDCA, glycohyodeoxycholic acid

3α,6α-dihydroxy-5β–cholan-24-oylglycine

GLCA, glycolithocholic acid

3α-hydroxy-5β–cholan-24-oylglycine

GLCAS

glycolithocholic acid sulfate

GUDCA, glycoursodeoxycholic acid

3α,7β-dihydroxy-5β–cholan-24-oylglycine

HCA, hyocholic acid

3α,6α,7α-trihydroxy-5β–cholan-24-oic acid

HDCA, hyodeoxycholic acid

3α,6α-dihydroxy-5β–cholan-24-oic acid

IS

internal standard

isoDCA, iso-deoxycholic acid

3β,12α-dihydroxy-5β–cholan-24-oic acid

isoLCA, iso-lithocholic acid

3β-hydroxy-5β–cholan-24-oic acid

LCA, lithocholic acid

3α-hydroxy-5β–cholan-24-oic acid

LCAS

lithocholic acid sulfate

αMCA, α-muricholic acid

3α,6β,7α-trihydroxy-5β–cholan-24-oic acid

βMCA, β-muricholic acid

3α,6β,7β-trihydroxy-5β–cholan-24-oic acid

ωMCA, ω-muricholic acid

3α,6a,7β-trihydroxy-5β–cholan-24-oic acid

MDCA, murideoxycholic acid, 3α

6β-dihydroxy-5β–cholan-24-oic acid

MRM

multiple reaction monitoring

m/z

mass to charge ratio

6-oxo-alloLCA

3α-hydroxy-6-oxo-5α–cholan-24-oic acid

12-oxoCDCA

3α,7α-dihydroxy-12-oxo-5β–cholan-24-oic acid

7-oxoDCA

3α,12α-dihydroxy-7-oxo-5β–cholan-24-oic acid

7-oxoHDCA

3α,6α-dihydroxy-7-oxo-5β–cholan-24-oic acid

6-oxoLCA

3α-hydroxy-6-oxo-5β–cholan-24-oic acid

7-oxoLCA

3α-hydroxy-7-oxo-5β–cholan-24-oic acid

12-oxoLCA

3α-hydroxy-12-oxo-5β–cholan-24-oic acid

TCA, taurocholic acid

3α,7α,12α–trihydroxy-5β–cholan-24-oyltaurine

TCA3S

taurocholic acid 3-sulfate

TCDCA, taurochenodeoxycholic acid

3α,7α-dihydroxy-5β–cholan-24-oyltaurine

TCDCA3S

taurochenodeoxycholic acid 3-sulfate

TDCA, taurodeoxycholic acid

3α,12α-dihydroxy-5β–cholan-24-oyltaurine

TDCA3S

taurodeoxycholic acid 3-sulfate

THCA, taurohyocholic acid

3α,6α,7α-trihydroxy-5β–cholan-24-oyltaurine

THDCA, taurohyodeoxycholic acid

3α,6α-dihydroxy-5β–cholan-24-oyltaurine

TLCA, taurolithocholic acid

3α-hydroxy-5β–cholan-24-oyltaurine

TLCAS

taurolithocholic acid sulfate

TαMCA, tauro-α-muricholic acid

3α,6β,7α-trihydroxy-5β–cholan-24-oyltaurine

TβMCA, tauro-β-muricholic acid

3α,6β,7β-trihydroxy-5β–cholan-24-oyltaurine

TωMCA, tauro-ω-muricholic acid

3α,6a,7β-trihydroxy-5β–cholan-24-oyltaurine

TMDCA, tauromurideoxycholic acid, 3α

6β-dihydroxy-5β–cholan-24-oyltaurine

TUDCA, tauroursodeoxycholic acid

3α,7β-dihydroxy-5β–cholan-24-oyltaurine

UDCA, ursodeoxycholic acid

3α,7β-dihydroxy-5β–cholan-24-oic acid

UPLC/MS/MS

ultra performance liquid chromatography-tandem mass spectrometry

WT

wild-type
This work was supported by National Institutes of Health Grants ES-009649, ES-013714, ES-009716, and RR-021940. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.
↵[S] The online version of this article (available at http://www.jlr.org) contains supplementary data in the form of an experimental procedure with 12 figures and one table.