Increased sulfation of bile acids in mice and human subjects with sodium taurocholate cotransporting polypeptide deficiency

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dc.contributor.authorMao, Fengfeng
dc.contributor.authorLiu, Teng
dc.contributor.authorHou, Xinfeng
dc.contributor.authorZhao, Hanqing
dc.contributor.authorHe, Wenhui
dc.contributor.authorLi, Cong
dc.contributor.authorJing, Zhiyi
dc.contributor.authorJianhua, Sui
dc.contributor.authorWang, Fengchao
dc.contributor.authorLiu, Xiaohui
dc.contributor.authorHan, Jun
dc.contributor.authorBorchers, Christoph H.
dc.contributor.authorWang, Jian-She
dc.contributor.authorLi, Wenhui
dc.date.accessioned2021-01-28T23:51:41Z
dc.date.available2021-01-28T23:51:41Z
dc.date.copyright2019en_US
dc.date.issued2019
dc.description.abstractSodium taurocholate cotransporting polypeptide (NTCP, encoded by Slc10a1/SLC10A1) 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 Slc10a1−/− mice, and we also assessed changes of TBA levels in 33 young individuals with SLC10A1 loss-of-function variant p.Ser267Phe. We found that overall serum TBA levels tended to decrease gradually with age in both Slc10a1−/− mice and p.Ser267Phe individuals. Liver mRNA profiling revealed notable transcription alterations in hypercholanemic Slc10a1−/− mice, including inhibition of bile acid (BA) synthesis, enhancement of BA detoxification, and altered BA transport. Members of the sulfotransferase (SULT) family showed the most dramatic increases in livers of hypercholanemic Slc10a1−/− mice, and one of their BA sulfates, taurolithocholic acid 3-sulfate, significantly increased. Importantly, consistent with the mouse studies, comprehensive profiling of 58 BA species in sera of p.Ser267Phe individuals revealed a markedly increased level of BA sulfates. Together, our findings indicate that the enhanced BA sulfation is a major mechanism for BA detoxification and elimination in both mice and humans with Slc10a1/SLC10A1 deficiency.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.identifier.citationMao, F., Liu, T., Hou, X., Zhao, H., He, W., Borchers, C. H., … Li, W. (2019). Increased sulfation of bile acids in mice and human subjects with sodium taurocholate cotransporting polypeptide deficiency. Journal of Biological Chemistry, 294(31), 11853-11862. https://doi.org/10.1074/jbc.RA118.007179.en_US
dc.identifier.urihttps://doi.org/10.1074/jbc.RA118.007179
dc.identifier.urihttp://hdl.handle.net/1828/12622
dc.language.isoenen_US
dc.publisherJournal of Biological Chemistryen_US
dc.subjectbile acid
dc.subjectsulfotransferase
dc.subjectliver metabolism
dc.subjectmass spectrometry (MS)
dc.subjectlipid metabolism
dc.subjectSLC10A1
dc.subjectsulfation
dc.subjecthypercholanemia
dc.subjectTLCA-3-sulfate
dc.subjectSult2a1
dc.subjectUVic Genome BC Proteomics Centre
dc.subject.departmentDivision of Medical Sciences
dc.subject.departmentSchool of Medical Sciences
dc.subject.departmentDepartment of Biochemistry and Microbiology
dc.titleIncreased sulfation of bile acids in mice and human subjects with sodium taurocholate cotransporting polypeptide deficiencyen_US
dc.typeArticleen_US

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