Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, Japan.
Department of Internal Medicine Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan.
Int J Mol Sci. 2022 Feb 4;23(3):1793. doi: 10.3390/ijms23031793.
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 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 levels, while downregulated phosphorylated ERK and levels in the liver. Likewise, taurine-treated Hepa1-6 cells, a mouse hepatocyte line, exhibited downregulated levels and upregulated promoter activity of . These results indicate that taurine promotes cholesterol metabolism by suppressing the FGF21/ERK pathway followed by upregulating expression. Collectively, this study shows that long-term feeding of taurine lowers both plasma cholesterol and bile acids, reinforcing that taurine effectively prevents hypercholesterolemia.
胆固醇是脊椎动物中的一种必需脂质，但血液中过量的胆固醇会促进动脉粥样硬化。在肝脏中，胆固醇通过细胞色素 P450 家族 7 亚家族 A 多肽 1（CYP7A1）代谢为胆汁酸，其转录受 ERK 通路的负调控。成纤维细胞生长因子 21（FGF21）是一种肝源细胞因子，可诱导 ERK 磷酸化并抑制转录。牛磺酸是一种含硫氨基酸，据报道可促进胆固醇代谢并降低血液和肝脏中的胆固醇水平。然而，长期摄入牛磺酸对胆固醇水平和代谢的影响尚不清楚。在这里，为了评估牛磺酸对胆固醇水平的更慢性影响，我们分析了喂养富含牛磺酸饮食 14-16 周的小鼠。长期喂养牛磺酸可降低血浆胆固醇和胆汁酸，而其他代谢参数无明显变化，但对肝脏中的这些水平几乎没有影响。此外，牛磺酸上调了水平，同时下调了肝脏中磷酸化 ERK 和的水平。同样，牛磺酸处理的 Hepa1-6 细胞（一种小鼠肝细胞系）表现出下调的水平和上调的启动子活性。这些结果表明，牛磺酸通过抑制 FGF21/ERK 通路来促进胆固醇代谢，随后上调的表达。总之，这项研究表明，长期摄入牛磺酸可降低血浆胆固醇和胆汁酸，这进一步证明了牛磺酸可有效预防高胆固醇血症。
