Sodium taurocholate cotransporting polypeptide (NTCP) is an important hepatocyte transporter, while its physiological functions require further investigation. In our study, an integrated plasma and liver GC-MS- and LC-MS-based metabolomics strategy with an optimized two-step liquid-liquid extraction was utilized to explore the physiological functions of NTCP via a knockout (KO) mouse model. The present study found that NTCP deficiency resulted in obvious metabolic change in the plasma and liver of mice. Totally, 102 and 87 differential metabolites were discovered in the liver and plasma, respectively. Pathway analysis revealed that the metabolism of tyrosine, glycine, taurine, fatty acid and glycerophospholipid as well as the biosynthesis of tryptophan, pantothenate and CoA were significantly dysregulated in the Ntcp KO mice, indicating that NTCP is closely involved in these metabolic pathways. Moreover, L-tryptophan, cadaverine and D-pantothenic acid could serve as the diagnostic biomarker for NTCP deficiency. Our study provided deep insights into the physiological functions of NTCP, and the findings would hold the great potential to be used for the discovery of new therapeutic and diagnostic strategies for NTCP deficiency clinically.

牛磺胆酸钠共转运多肽（NTCP）是重要的肝细胞转运蛋白，但其生理功能需要进一步研究。在我们的研究中，利用整合的血浆和肝脏基于GC-MS和LC-MS的代谢组学策略，以及经过优化的两步液-液萃取，通过敲除（KO）小鼠模型探索NTCP的生理功能。本研究发现，NTCP缺乏会导致小鼠血浆和肝脏中明显的代谢变化。总共在肝脏和血浆中分别发现了102和87种差异代谢物。通路分析表明，Ntcp中酪氨酸，甘氨酸，牛磺酸，脂肪酸和甘油磷脂的代谢以及色氨酸，泛酸和CoA的生物合成明显失调。KO小鼠，表明NTCP与这些代谢途径密切相关。此外，L-色氨酸，尸胺和D-泛酸可作为NTCP缺乏的诊断生物标志物。我们的研究为NTCP的生理功能提供了深刻的见解，这些发现将具有巨大的潜力，可用于临床上发现NTCP缺乏症的新治疗和诊断策略。