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

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 expressio...

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Published in:Cells (Basel, Switzerland) Switzerland), 2022-07, Vol.11 (14), p.2159
Main Authors: Lai, Qi, Ma, Yanhua, Bai, Jin, Zhuang, Min, Pei, Shaofei, He, Ni, Yin, Junlin, Fan, Baomin, Bian, Zhaoxiang, Zeng, Guangzhi, Lin, Chengyuan
Format: Article
Language:English
Subjects:
Acids
Adenylate cyclase
Bile
bile acid
Bile acids
Cell lines
Chenodeoxycholic acid
Cholesterol
Cyclic AMP
Deoxycholic acid
Diabetes
Gene expression
gene transcription
Gluconeogenesis
Glucose metabolism
Glycolysis
Hydroxylase
Ileum
Insulin resistance
Kinases
Lipid metabolism
Lipids
Liver
liver cells
MAP kinase
Metabolism
Obesity
Pathogenesis
Protein kinase A
Proteins
Small intestine
spexin
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Summary: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.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells11142159