Grant: Project Grant

Vitamin A is an essential part of our diet and is used by the body in many ways, including vision, immunity and reproduction. The liver acts as a warehouse for vitamin A: storing it and releasing it for use in other parts of the body. Vitamin A is also important in maintaining liver health, and it has been suggested that a disruption in this role promotes the development of liver disease. Alcohol abuse is a major cause of preventable death and gives rise to a significant disease burden in Canada. The main organ affected by drinking too much alcohol is the liver, with a well-described disease response ranging from fat accumulation (steatosis), to inflammation (hepatitis), scarring (fibrosis and cirrhosis) and ultimately liver failure. According to the Canadian Liver Foundation, approximately 1 in 12 Canadians drink heavily, and thousands of Canadians die every year because of alcoholic liver disease, making it a national research priority. Moreover, heavy drinking rates are double for First Nations people living on Reserves, representing a population at increased risk of alcohol-related disease. The research described in this proposal aims to establish that alcohol disturbs the way vitamin A works in the liver, contributing to hepatic disease. Through a series of complementary experiments, we will determine the mechanism through which alcohol disturbs vitamin A function at two points in the disease process: 1) the initial step of fat accumulation, and 2) the formation of scar tissue, representing the worsening of liver disease. This research will provide a better understanding of how alcohol causes liver disease by disrupting vitamin A function. The new knowledge generated by this research may be translated into improved care for heavy drinkers at risk of alcoholic liver disease by providing ways to prevent its formation, or stop it from worsening. This knowledge will also provide new insight into how altered vitamin A function contributes to other human diseases.