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

Fengfeng Mao, Teng Liu, Xinfeng Hou, Hanqing Zhao, Wenhui He, Cong Li, Zhiyi Jing, Jianhua Sui, Fengchao Wang, Xiaohui Liu, Jun Han, Christoph H. Borchers, Jian She Wang, Wenhui Li

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Sodium 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.

Original languageEnglish
Pages (from-to)11853-11862
Number of pages10
JournalJournal of Biological Chemistry
Volume294
Issue number31
DOIs
Publication statusPublished - 2 Aug 2019
Externally publishedYes

Fingerprint

Dive into the research topics of 'Increased sulfation of bile acids in mice and human subjects with sodium taurocholate cotransporting polypeptide deficiency'. Together they form a unique fingerprint.

Cite this