Hepatic free cholesterol accumulates in obese, diabetic mice and causes nonalcoholic steatohepatitis.

ABSTRACT:

Background & aims

Type 2 diabetes and nonalcoholic steatohepatitis (NASH) are associated with insulin resistance and disordered cholesterol homeostasis. We investigated the basis for hepatic cholesterol accumulation with insulin resistance and its relevance to the pathogenesis of NASH.

Methods

Alms1 mutant (foz/foz) and wild-type NOD.B10 mice were fed high-fat diets that contained varying percentages of cholesterol; hepatic lipid pools and pathways of cholesterol turnover were determined. Hepatocytes were exposed to insulin concentrations that circulate in diabetic foz/foz mice.

Results

Hepatic cholesterol accumulation was attributed to up-regulation of low-density lipoprotein receptor via activation of sterol regulatory element binding protein 2 (SREBP-2), reduced bi

SUBMITTER: Van Rooyen DM 

PROVIDER: S-EPMC3186822 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature