Hyperlipidemia is characterized by elevated levels of cholesterol and triglycerides and is increasingly prevalent as humans age. Hyperlipidemia has been strongly correlated with heart disease, but its role in other diseases has not been extensively studied. Recent data from our laboratory shows that liver damage develops with age in the hyperlipidemic environment of transgenic mice that overexpress the human apolipoprotein (apo) C-I gene. ApoC-I mice have hyperlipidemia due to impaired lipoprotein clearance, and chronically elevated lipoprotein levels have been associated with the onset of damage to the arterial walls in heart disease. The onset of liver damage seen in our mouse model may be initiated by this condition as well. It is hypothesized that impaired lipoprotein clearance caused by persistent hyperlipidemia leads to oxidative modification of the lipoproteins by reactive oxygen species (ROS). Oxidatively modified lipoproteins may initiate damage to the liver that gets progressively worse with age. It is also hypothesized that caloric restriction of hyperlipidemic mice will be effective in reducing lipid levels. This reduction will result in a substantial decrease in both the oxidative modification of lipoprotems and subsequent liver damage.
