ORP2 regulates free cholesterol accumulation in hepatocytes during MASH.

ABSTRACT:

Background

Cholesterol crystals in hepatocytes are known to strongly associate with human metabolic dysfunction-associated steatohepatitis. However, it remains unclear which molecular pathway(s) regulates free cholesterol accumulation and the formation of cholesterol crystals in hepatocytes. In cultured cell lines, oxysterol-binding protein-related protein 2 (ORP2) functions to deliver cholesterol to the plasma membrane from endosomal compartments.

Methods

Here, we generated liver-specific ORP2 knockout (ORP2-LKO) mice and characterized their metabolic phenotypes on chow and high-fat diet.

Results

The ORP2-LKO mice developed much more severe hepatic steatosis than floxed control mice after high-fat diet feeding. They also demonstrated more severe liver inflammation an

SUBMITTER: Wu J 

PROVIDER: S-EPMC12262990 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature