Palmitate-induced activation of mitochondrial metabolism promotes oxidative stress and apoptosis in H4IIEC3 rat hepatocytes.

ABSTRACT:

Objective

Hepatic lipotoxicity is characterized by reactive oxygen species (ROS) accumulation, mitochondrial dysfunction, and excessive apoptosis, but the precise sequence of biochemical events leading to oxidative damage and cell death remains unclear. The goal of this study was to delineate the role of mitochondrial metabolism in mediating hepatocyte lipotoxicity.

Materials/methods

We treated H4IIEC3 rat hepatoma cells with free fatty acids in combination with antioxidants and mitochondrial inhibitors designed to block key events in the progression toward apoptosis. We then applied (13)C metabolic flux analysis (MFA) to quantify mitochondrial pathway alterations associated with these treatments.

Results

Treatment with palmitate alone led to a doubling in oxygen upta

SUBMITTER: Egnatchik RA 

PROVIDER: S-EPMC3946971 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature