The objectives of this research project are to determine the effects of certain nutritional, hormonal, and genetic factors on the composition and metabolism of lipoproteins in squirrel and rhesus monkey and rabbits. In squirrel monkeys the feeding of diets with saturated fats and cholesterol results in the development of atherosclerosis and cholesterol gallstones. One population with low levels of high density 2 lipoproteins (HDL2) is resistant to gallstone formation. We are measuring lipoprotein levels and compositions and determining turnover characteristics of different components of the lipoproteins and bile composition and formation by the gallstone susceptible and resistant populations. The levels of dietary protein influence the concentrations and metabolism of very low density lipoprotein and HDL2 in rhesus monkeys. We are doing experiments to explain the mechanisms. Lastly, we are studing the interaction of lipoprotein apoproteins and lipids with primary cultures of rabbit hepatocytes to determine the extent of intact lipoprotein uptake and lipid exchange between lipoproteins and cells, and the factors that control those processes.