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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MDPI AG
2022-07-01
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| author | Qi Lai Yanhua Ma Jin Bai Min Zhuang Shaofei Pei Ni He Junlin Yin Baomin Fan Zhaoxiang Bian Guangzhi Zeng Chengyuan Lin |
| author_facet | Qi Lai Yanhua Ma Jin Bai Min Zhuang Shaofei Pei Ni He Junlin Yin Baomin Fan Zhaoxiang Bian Guangzhi Zeng Chengyuan Lin |
| author_sort | Qi Lai |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T03:35:18Z |
| format | Article |
| id | doaj.art-2ad6cb190bc24f6a977bc06167e332b4 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T03:35:18Z |
| publishDate | 2022-07-01 |
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| series | Cells |
| spelling | doaj.art-2ad6cb190bc24f6a977bc06167e332b42023-12-03T14:49:37ZengMDPI AGCells2073-44092022-07-011114215910.3390/cells11142159Mechanisms for Bile Acids CDCA- and DCA-Stimulated Hepatic Spexin ExpressionQi Lai0Yanhua Ma1Jin Bai2Min Zhuang3Shaofei Pei4Ni He5Junlin Yin6Baomin Fan7Zhaoxiang Bian8Guangzhi Zeng9Chengyuan Lin10Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, School of Ethnic Medicine, Yunnan Minzu University, Kunming 650504, ChinaKey Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, School of Ethnic Medicine, Yunnan Minzu University, Kunming 650504, ChinaDepartment of Obstetrics and Gynecology, University of California Irvine, Irvine, CA 92697, USAKey Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, School of Ethnic Medicine, Yunnan Minzu University, Kunming 650504, ChinaKey Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, School of Ethnic Medicine, Yunnan Minzu University, Kunming 650504, ChinaKey Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, School of Ethnic Medicine, Yunnan Minzu University, Kunming 650504, ChinaKey Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, School of Ethnic Medicine, Yunnan Minzu University, Kunming 650504, ChinaKey Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, School of Ethnic Medicine, Yunnan Minzu University, Kunming 650504, ChinaCentre for Chinese Herbal Medicine Drug Development Limited, Hong Kong Baptist University, Hong Kong, ChinaKey Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, School of Ethnic Medicine, Yunnan Minzu University, Kunming 650504, ChinaCentre for Chinese Herbal Medicine Drug Development Limited, Hong Kong Baptist University, Hong Kong, ChinaSpexin (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.https://www.mdpi.com/2073-4409/11/14/2159spexinbile acidliver cellsgene transcription |
| spellingShingle | Qi Lai Yanhua Ma Jin Bai Min Zhuang Shaofei Pei Ni He Junlin Yin Baomin Fan Zhaoxiang Bian Guangzhi Zeng Chengyuan Lin Mechanisms for Bile Acids CDCA- and DCA-Stimulated Hepatic Spexin Expression Cells spexin bile acid liver cells gene transcription |
| title | Mechanisms for Bile Acids CDCA- and DCA-Stimulated Hepatic Spexin Expression |
| title_full | Mechanisms for Bile Acids CDCA- and DCA-Stimulated Hepatic Spexin Expression |
| title_fullStr | Mechanisms for Bile Acids CDCA- and DCA-Stimulated Hepatic Spexin Expression |
| title_full_unstemmed | Mechanisms for Bile Acids CDCA- and DCA-Stimulated Hepatic Spexin Expression |
| title_short | Mechanisms for Bile Acids CDCA- and DCA-Stimulated Hepatic Spexin Expression |
| title_sort | mechanisms for bile acids cdca and dca stimulated hepatic spexin expression |
| topic | spexin bile acid liver cells gene transcription |
| url | https://www.mdpi.com/2073-4409/11/14/2159 |
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