Hepatic management of toxic sterols after acute deletion of Cyp51 from cholesterol synthesis.

ABSTRACT: Lanosterol 14α-demethylase (CYP51), a key enzyme in cholesterol synthesis, is essential for normal liver function. Reduced CYP51 activity leads to metabolism-associated liver disease and ultimately hepatocellular carcinoma, yet the hepatocellular processes most affected and their crosstalk with other liver cell types remain poorly defined. Here, we present a new inducible liver-specific Cyp51 KO mouse (iLKO) model designed to study how acute disruption of cholesterol synthesis is managed in the adult liver. Doxycycline-inducible deletion minimizes developmental confounders of albumin-Cre models and enables isolation of viable primary hepatocytes. iLKO hepatocytes and liver tissue showed efficient CYP51 depletion with marked accumulation of lanosterol and 24,25-dihydrolanosterol, whereas he

SUBMITTER: Kreft T 

PROVIDER: S-EPMC12930059 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature