Mechanisms for Bile Acids CDCA- and DCA-Stimulated Hepatic Spexin Expression

Qi Lai, Yanhua Ma, Jin Bai, Min Zhuang, Shaofei Pei, Ni He, Junlin Yin, Baomin Fan, Zhaoxiang Bian, Guangzhi Zeng*, Chengyuan Lin*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

6 Citations (Scopus)

Abstract

Spexin (SPX) is a novel peptide involved in glucose and lipid metabolism and suppresses hepatic total bile acid levels by inhibiting hepatic cholesterol 7α-hydroxylase 1 expression. As important mediators for glycolysis/gluconeogenesis and lipid metabolism, the effects of bile acids on SPX expression is yet to be understood. By using SMMC7721 and BEL-7402 cell lines, we screened the effects of bile acids and found that chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) can stimulate SPX gene transcription. Both CDCA and DCA were able to stimulate SPX mRNA expression in the liver but not colon and ileum in mice. In SMMC7721 and BEL-7402 cells, CDCA- and DCA-induced SPX promoter activity was mimicked by bile acid receptor FXR and TGR5 activation and suppressed by FXR and TGR5 silencing. Adenylate cyclase (AC)/cyclic adenosine monophosphate (cAMP) activators significantly increased SPX promoter activity whereas the inhibitors for AC/CAMP/protein kinase A (PKA) and mitogen-activated protein kinases (MAPK) pathway attenuated CDCA- and DCA-induced SPX transcription. Thus, CDCA and DCA stimulate SPX expression at the hepatic level through FXR and TGR5 mediated AC/cAMP/PKA and MAPK cascades.

Original languageEnglish
JournalCells
Volume11
Issue number14
DOIs
Publication statusPublished - 10 Jul 2022

User-Defined Keywords

  • Animals
  • Bile Acids and Salts/metabolism
  • Chenodeoxycholic Acid/pharmacology
  • Cholesterol 7-alpha-Hydroxylase/metabolism
  • Cyclic AMP/metabolism
  • Cyclic AMP-Dependent Protein Kinases/metabolism
  • Liver/metabolism
  • Mice
  • Peptide Hormones/genetics
  • Promoter Regions, Genetic/genetics

Fingerprint

Dive into the research topics of 'Mechanisms for Bile Acids CDCA- and DCA-Stimulated Hepatic Spexin Expression'. Together they form a unique fingerprint.

Cite this