Long-Term Dietary Taurine Lowers Plasma Levels of Cholesterol and Bile Acids
Cholesterol is an essential lipid in vertebrates, but excess blood cholesterol promotes atherosclerosis. In the liver, cholesterol is metabolized to bile acids by cytochrome P450, family 7, subfamily a, polypeptide 1 (CYP7A1), the transcription of which is negatively regulated by the ERK pathway. Fi...
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2022-02-01
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author | Ryoma Tagawa Masaki Kobayashi Misako Sakurai Maho Yoshida Hiroki Kaneko Yuhei Mizunoe Yuka Nozaki Naoyuki Okita Yuka Sudo Yoshikazu Higami |
author_facet | Ryoma Tagawa Masaki Kobayashi Misako Sakurai Maho Yoshida Hiroki Kaneko Yuhei Mizunoe Yuka Nozaki Naoyuki Okita Yuka Sudo Yoshikazu Higami |
author_sort | Ryoma Tagawa |
collection | DOAJ |
description | Cholesterol is an essential lipid in vertebrates, but excess blood cholesterol promotes atherosclerosis. In the liver, cholesterol is metabolized to bile acids by cytochrome P450, family 7, subfamily a, polypeptide 1 (CYP7A1), the transcription of which is negatively regulated by the ERK pathway. Fibroblast growth factor 21 (FGF21), a hepatokine, induces ERK phosphorylation and suppresses <i>Cyp7a1</i> transcription. Taurine, a sulfur-containing amino acid, reportedly promotes cholesterol metabolism and lowers blood and hepatic cholesterol levels. However, the influence of long-term feeding of taurine on cholesterol levels and metabolism remains unclear. Here, to evaluate the more chronic effects of taurine on cholesterol levels, we analyzed mice fed a taurine-rich diet for 14–16 weeks. Long-term feeding of taurine lowered plasma cholesterol and bile acids without significantly changing other metabolic parameters, but hardly affected these levels in the liver. Moreover, taurine upregulated <i>Cyp7a1</i> levels, while downregulated phosphorylated ERK and <i>Fgf21</i> levels in the liver. Likewise, taurine-treated Hepa1-6 cells, a mouse hepatocyte line, exhibited downregulated <i>Fgf21</i> levels and upregulated promoter activity of <i>Cyp7a1</i>. These results indicate that taurine promotes cholesterol metabolism by suppressing the FGF21/ERK pathway followed by upregulating <i>Cyp7a1</i> expression. Collectively, this study shows that long-term feeding of taurine lowers both plasma cholesterol and bile acids, reinforcing that taurine effectively prevents hypercholesterolemia. |
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spelling | doaj.art-4df88fd97b354361aa031b2b69e2a8652023-11-23T16:46:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01233179310.3390/ijms23031793Long-Term Dietary Taurine Lowers Plasma Levels of Cholesterol and Bile AcidsRyoma Tagawa0Masaki Kobayashi1Misako Sakurai2Maho Yoshida3Hiroki Kaneko4Yuhei Mizunoe5Yuka Nozaki6Naoyuki Okita7Yuka Sudo8Yoshikazu Higami9Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, JapanDepartment of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, JapanDepartment of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, JapanDepartment of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, JapanDepartment of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, JapanDepartment of Internal Medicine Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, JapanDepartment of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, JapanDivision of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Yamaguchi 756-0884, JapanDepartment of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, JapanDepartment of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, JapanCholesterol is an essential lipid in vertebrates, but excess blood cholesterol promotes atherosclerosis. In the liver, cholesterol is metabolized to bile acids by cytochrome P450, family 7, subfamily a, polypeptide 1 (CYP7A1), the transcription of which is negatively regulated by the ERK pathway. Fibroblast growth factor 21 (FGF21), a hepatokine, induces ERK phosphorylation and suppresses <i>Cyp7a1</i> transcription. Taurine, a sulfur-containing amino acid, reportedly promotes cholesterol metabolism and lowers blood and hepatic cholesterol levels. However, the influence of long-term feeding of taurine on cholesterol levels and metabolism remains unclear. Here, to evaluate the more chronic effects of taurine on cholesterol levels, we analyzed mice fed a taurine-rich diet for 14–16 weeks. Long-term feeding of taurine lowered plasma cholesterol and bile acids without significantly changing other metabolic parameters, but hardly affected these levels in the liver. Moreover, taurine upregulated <i>Cyp7a1</i> levels, while downregulated phosphorylated ERK and <i>Fgf21</i> levels in the liver. Likewise, taurine-treated Hepa1-6 cells, a mouse hepatocyte line, exhibited downregulated <i>Fgf21</i> levels and upregulated promoter activity of <i>Cyp7a1</i>. These results indicate that taurine promotes cholesterol metabolism by suppressing the FGF21/ERK pathway followed by upregulating <i>Cyp7a1</i> expression. Collectively, this study shows that long-term feeding of taurine lowers both plasma cholesterol and bile acids, reinforcing that taurine effectively prevents hypercholesterolemia.https://www.mdpi.com/1422-0067/23/3/1793taurinecholesterolbile acidFGF21ERKCYP7A1 |
spellingShingle | Ryoma Tagawa Masaki Kobayashi Misako Sakurai Maho Yoshida Hiroki Kaneko Yuhei Mizunoe Yuka Nozaki Naoyuki Okita Yuka Sudo Yoshikazu Higami Long-Term Dietary Taurine Lowers Plasma Levels of Cholesterol and Bile Acids International Journal of Molecular Sciences taurine cholesterol bile acid FGF21 ERK CYP7A1 |
title | Long-Term Dietary Taurine Lowers Plasma Levels of Cholesterol and Bile Acids |
title_full | Long-Term Dietary Taurine Lowers Plasma Levels of Cholesterol and Bile Acids |
title_fullStr | Long-Term Dietary Taurine Lowers Plasma Levels of Cholesterol and Bile Acids |
title_full_unstemmed | Long-Term Dietary Taurine Lowers Plasma Levels of Cholesterol and Bile Acids |
title_short | Long-Term Dietary Taurine Lowers Plasma Levels of Cholesterol and Bile Acids |
title_sort | long term dietary taurine lowers plasma levels of cholesterol and bile acids |
topic | taurine cholesterol bile acid FGF21 ERK CYP7A1 |
url | https://www.mdpi.com/1422-0067/23/3/1793 |
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