TNAP dephosphorylates phosphocholine and phosphoethanolamine and participates in triglyceride transport from the liver to the bloodstream.

ABSTRACT: Tissue-nonspecific alkaline phosphatase (TNAP) is primarily known for its role in skeletal mineralization, through the hydrolysis of inorganic pyrophosphate (PP_i). Here we demonstrate that TNAP-knockout mice exhibit liver steatosis and reduced serum triglyceride levels, mirroring the effects of choline deficiency, which impairs phosphatidylcholine synthesis, an essential component of VLDL. In fasting WT mice, TNAP inhibition via SBI-425 administration decreases choline levels in blood and liver. Incubating mouse or human serum with SBI-425 inhibits the dephosphorylation of phosphocholine and phosphoethanolamine, an alternative substrate for hepatic phosphatidylcholine synthesis. In hepatocytes, TNAP inhibition impedes proliferation when the medium is supplemented with phosphocho

SUBMITTER: Drevet Mulard E 

PROVIDER: S-EPMC12559424 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature