The physiological blood concentration of phenylalanine-proline can ameliorate cholesterol metabolism in HepG2 cells.
The physiological blood concentration of phenylalanine-proline can ameliorate cholesterol metabolism in HepG2 cells.
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苯丙氨酸脯氨酸的生理血液浓度可以改善HepG2细胞中的胆固醇代谢。
DOI：
10.1093/bbb/zbac167
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发表时间：
2023
期刊：
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S.:
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作者：
Banno;A.;Yamamoto;M.;Mijiti;M.;Takeuchi;A.;Ye;Y.;Oda;N.;Nishino;N.;Ebihara;A.; Nagaoka;S.:
我们以前曾报道过二肽Phe-Pro影响体内和体外的脂质代谢，但关于Phe-Pro通过PepT 1被肠道吸收后的作用机制知之甚少。在这项研究中，我们给予大鼠单次口服剂量的Phe-Pro，并使用LC-TOF/MS分析定量其在门静脉血浆中的浓度。此外，将生理血液浓度的Phe-Pro加入HepG 2细胞的脂质蓄积模型中，以降低细胞内胆固醇并增加CYP 7A 1和PPARα mRNA水平的表达。此外，我们使用AlphaFold 2分析了PPARα和Phe-Pro的结合。我们发现Phe-Pro是PPARα的配体。据我们所知，这是第一项研究表明Phe-Pro存在于门静脉血浆中。我们首次发现Phe-Pro改善HepG 2细胞的胆固醇代谢。
We have previously reported that the dipeptide Phe-Pro affects lipid metabolismin vivoandin vitro, but very little is known regarding the mechanism of action of Phe-Pro after it is absorbed by the intestines via PepT1. In this study, we administered a single oral dose of Phe-Pro to rats and quantified its concentration in the portal plasma using LC-TOF/MS analysis. Additionally, the physiological blood concentration of Phe-Pro was added to the lipid accumulation model of HepG2 cells to decrease intracellular cholesterol and increase the expression of CYP7A1 and PPARα mRNA levels. Moreover, we analyzed the binding of PPARα and Phe-Pro using AlphaFold2. We found that Phe-Pro is a ligand for PPARα. To the best of our knowledge, this is the first study that shows Phe-Pro to be present in the portal plasma. We found for the first time that Phe-Pro ameliorated cholesterol metabolism in HepG2 cells.