Effect of cholesterol overload on gene expression of hepatic macrophages isolated from normal and NASH livers.

ABSTRACT: Hepatocyte death plays a critical role in the disease progression from simple steatosis to non-alcoholic steatohepatitis (NASH). We have previously reported that hepatocyte death locally induces phenotypic changes in the macrophages surrounding the corpse and remnant lipids, thereby promoting liver fibrosis in a murine model of NASH. Here, we demonstrated free cholesterol was accumulated in macrophages around dead hepatocytes containing cholesterol crystals. In vitro experiments revealed that cholesterol-induced lysosomal stress triggered profibrotic activation in macrophages predisposed to the steatotic microenvironment. This study provides evidence that dysregulated cholesterol metabolism in macrophages would be a novel mechanism of NASH.

ORGANISM(S): Mus musculus

PROVIDER: GSE235024 | GEO | 2023/06/20

REPOSITORIES: GEO