Cholesterol overload in macrophages drives metabolic dysfunction-associated steatohepatitis via inhibiting 7-dehydrocholesterol reductase in mice.

ABSTRACT:

Background

Dietary cholesterol promotes metabolic dysfunction-associated steatohepatitis (MASH), with hepatic macrophages central to disease pathology. However, the mechanisms by which cholesterol-loaded macrophages influence MASH remain unclear.

Methods

In this study, mice were fed a cholesterol-rich choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). Hepatic cholesterol levels, inflammatory markers, and pro-inflammatory macrophage polarization were assessed. In vitro studies examined the impact of cholesterol on macrophage polarization, identifying 7-dehydrocholesterol reductase (DHCR7) as a key cholesterol- and inflammation-responsive enzyme. DHCR7 expression in macrophages from MASH patients and model mice was evaluated. Functional studies involving in vitro

SUBMITTER: Li X 

PROVIDER: S-EPMC11605946 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature