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Cysteine sulfinic acid decarboxylase regulation: A role for farnesoid X receptor and small heterodimer partner in murine hepatic taurine metabolism
Author(s) -
Kerr Thomas A.,
Matsumoto Yuri,
Matsumoto Hitoshi,
Xie Yan,
Hirschberger Lawrence L.,
Stipanuk Martha H.,
Anakk Sayeepriyadarshini,
Moore David D.,
Watanabe Mitsuhiro,
Kennedy Susan,
Davidson Nicholas O.
Publication year - 2014
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/hepr.12230
Subject(s) - farnesoid x receptor , taurine , cysteine , sulfinic acid , biochemistry , chemistry , metabolism , receptor , nuclear receptor , enzyme , amino acid , transcription factor , gene , organic chemistry
Aim Bile acid synthesis is regulated by nuclear receptors including farnesoid X receptor ( FXR ) and small heterodimer partner ( SHP ), and by fibroblast growth factor 15/19 ( FGF 15/19). We hypothesized that hepatic cysteine sulfinic acid decarboxylase ( CSAD ) (a key enzyme in taurine synthesis) is regulated by bile acids ( BA ). The aim of this study was to investigate CSAD regulation by BA dependent regulatory mechanisms. Methods Mice were fed a control diet or a diet supplemented with either 0.5% cholate or 2% cholestyramine. To study BA dependent pathways, we utilized GW 4064 ( FXR agonist), FGF 19 or T ‐0901317 (liver X receptor [ LXR ] agonist) and Shp −/− mice. Tissue m RNA was determined by quantitative reverse transcription polymerase chain reaction. Amino acids were measured by high‐performance liquid chromatography. Results Mice supplemented with dietary cholate exhibited reduced hepatic CSAD m RNA while those receiving cholestyramine exhibited increased m RNA . Activation of FXR suppressed CSAD m RNA expression whereas CSAD expression was increased in Shp −/− mice. Hepatic hypotaurine concentration (the product of CSAD ) was higher in Shp −/− mice with a corresponding increase in serum taurine conjugated BA . FGF 19 administration suppressed hepatic cholesterol 7‐α‐hydroxylase ( CYP7A1 ) m RNA but did not change CSAD m RNA expression. LXR activation induced CYP7A1 m RNA yet failed to induce CSAD m RNA expression. Conclusion BA regulate CSAD m RNA expression in a feedback fashion via mechanisms involving SHP and FXR but not FGF 15/19 or LXR . These findings implicate BA as regulators of CSAD m RNA via mechanisms shared with CYP7A1 .