Novel oral SPT inhibitor CH5169356 inhibits hepatic stellate cell activation and ameliorates hepatic fibrosis in mouse models of non-alcoholic steatohepatitis (NASH).

ABSTRACT: Ceramide is a central molecule of sphingolipid metabolism and is involved in the development of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). It has already been reported that the inhibition of serine palmitoyltransferase (SPT), the rate-limiting enzyme in the sphingolipid biosynthetic pathway, has an inhibitory effect on hepatic lipidosis, but its effect on severe hepatic fibrosis is not clear. In this study, we examined whether a SPT inhibitor could suppress the activation of hepatic stellate cells (HSC) and ameliorate the progression of NASH. Effects on sphingolipid metabolism and HSC activation marker genes by NA808, a SPT inhibitor, were evaluated in an immortalized HSC cell line (E14C12). NA808 decreased sphingolipid synthesis and the expression

SUBMITTER: Hada N 

PROVIDER: S-EPMC10197225 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature