biostudies-literatureMao FScience and Technology Major Project of BeijingLeading Edge Endowment Fund (University of Victoria) and the Segal McGill Chair in Molecular Oncology at McGill UniversityWarren Y. Soper Charitable Trust and Alvin Segal Family Foundation to the Jewish General HospitalNational Natural Science Foundation of China (NSFC)Metabolomics Innovation CentreChina Scholarship Council (CSC)Science and Technology Bureau of Beijing Municipal Government11853-11862https://www.ebi.ac.uk/biostudies/studies/S-EPMC6682732biostudies-literatureUnknown294(31)Sodium taurocholate cotransporting polypeptide (NTCP, encoded by <i>Slc10a1</i>/<i>SLC10A1</i>) deficiency can result in hypercholanemia but no obvious symptoms in both mice and humans. However, the consequence of and response to long-term hypercholanemia caused by NTCP deficiency remain largely unexplored. Here, we analyzed lifelong dynamics of serum total bile acid (TBA) levels in <i>Slc10a1</i> ^-/- mice, and we also assessed changes of TBA levels in 33 young individuals with <i>SLC10A1</i> loss-of-function variant p.Ser267Phe. We found that overall serum TBA levels tended to decrease gradually with age in both <i>Slc10a1</i> ^-/- mice and p.Ser267Phe individuals. Liver mRNA profiling revealed notable transcription alterations in hypercholanemic <i>Slc10a1</i> <sup>-The Journal of biological chemistryIncreased sulfation of bile acids in mice and human subjects with sodium taurocholate cotransporting polypeptide deficiency.PMC668273281570468D171100003117003MC3T81525018720381741056Warren Y. Soper Charitable Trust and Alvin Segal Family Foundation215MET205MET201606100226Li CWang JSWang FMao FLiu THou XLiu XLi WBorchers CHJing ZHe WSui JHan JZhao HfalseIncreased sulfation of bile acids in mice and human subjects with sodium taurocholate cotransporting polypeptide deficiency.Sodium taurocholate cotransporting polypeptide (NTCP, encoded by <i>Slc10a1</i>/<i>SLC10A1</i>) deficiency can result in hypercholanemia but no obvious symptoms in both mice and humans. However, the consequence of and response to long-term hypercholanemia caused by NTCP deficiency remain largely unexplored. Here, we analyzed lifelong dynamics of serum total bile acid (TBA) levels in <i>Slc10a1</i> ^-/- mice, and we also assessed changes of TBA levels in 33 young individuals with <i>SLC10A1</i> loss-of-function variant p.Ser267Phe. We found that overall serum TBA levels tended to decrease gradually with age in both <i>Slc10a1</i> ^-/- mice and p.Ser267Phe individuals. Liver mRNA profiling revealed notable transcription alterations in hypercholanemic <i>Slc10a1</i> <sup>-2019-01-01T00:00:00Z2019 Aug2025-04-06T19:33:36.061Z2025-04-06T19:33:36.061ZS-EPMC66827323120127210.1074/jbc.RA118.00717910.1074/jbc.ra118.007179