High fat diet induced hepatic steatosis and insulin resistance: Role of dysregulated ceramide metabolism.

ABSTRACT:

Aim

  Non-alcoholic fatty liver disease (NAFLD) is an insulin resistance disease that can progress to cirrhosis and liver failure. We hypothesized that in NAFLD, insulin resistance dysregulates lipid metabolism, increasing production of cytotoxic lipids including ceramides, which exacerbate hepatic insulin resistance and injury.

Methods

  Long Evans rats were pair-fed low (LFD) or high (HFD) fat diets for 8 weeks. Livers were used to measure lipids, gene expression, insulin receptor binding, integrity of insulin signaling, and pro-inflammatory cytokines. In vitro experiments characterized effects of ceramides on Huh7 cell viability, mitochondrial function, and insulin signaling.

Results

  High fat diet feeding caused NAFLD with peripheral and hepatic insulin resistanc

SUBMITTER: Longato L 

PROVIDER: S-EPMC4096625 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature