Structural determinants of hepatic apolipoprotein B metabolism

Lipoproteins are complexes of protein and dietary fat that are important in the distribution of food energy in the bloodstream. However, when fats are consumed in excess, they can cause the liver to produce even more lipoproteins. The liver produces a carrier protein, called apolipoprotein B, which binds and transports cholesterol and dietary fats in the bloodstream and delivers them to sites in the body where they are needed for proper growth and nutrition. If these complexes are produced in excess and accumulate in the blood they can cause atherosclerosis, or "hardening", of the blood vessels. My research is trying to understand how the liver controls how much lipoprotein is made in the liver and transported into the blood and how the natural breakdown of apolipoprotein B can affect this control. We want to identify the components of this removal system that might be specific for the apolipoprotein B. The fat binding properties of this protein may be important in determining how the liver responds to and complexes with excess dietary fat as well as how the protein is destroyed if fat is not present. We are working to understand how the structures in the apolipoprotein B interact with dietary fat and other proteins in the liver, in an effort to understand how certain foods and drugs might be used to reduce the blood levels of lipoproteins and the progression of vascular diseases.