Bile Acid Sequestrant, Sevelamer Ameliorates Hepatic Fibrosis with Reduced Overload of Endogenous Lipopolysaccharide in Experimental Nonalcoholic Steatohepatitis.

ABSTRACT: Despite the use of various pharmacotherapeutic strategies, fibrosis due to nonalcoholic steatohepatitis (NASH) remains an unsatisfied clinical issue. We investigated the effect of sevelamer, a hydrophilic bile acid sequestrant, on hepatic fibrosis in a murine NASH model. Male C57BL/6J mice were fed a choline-deficient, L-amino acid-defined, high-fat (CDHF) diet for 12 weeks with or without orally administered sevelamer hydrochloride (2% per diet weight). Histological and biochemical analyses revealed that sevelamer prevented hepatic steatosis, macrophage infiltration, and pericellular fibrosis in CDHF-fed mice. Sevelamer reduced the portal levels of total bile acid and inhibited both hepatic and intestinal farnesoid X receptor activation. Gut microbiome analysis demonstrated that sevelamer

SUBMITTER: Tsuji Y 

PROVIDER: S-EPMC7357162 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature