The goals of this proposal are to study the apoprotein and the lipid compositions of hepatic lymph lipoproteins, and also to characterize the hepatic lymph cannulated rat as an in vivo model for studying lipoprotein secretion by the liver. To achieve these goals, we will first finish characterizing the apoprotein and lipid composition of hepatic lymph and its lipoproteins. Then, by using the isolated perfused liver but with the hepatic lymph duct cannulated, we will measure the quantity and the type of lipoproteins secreted into the lymph and the perfusate (i.e., the vascular pathway) under normal and experimental conditions which are known to modify hepatic VLDL production. We will also measure the contribution of plasma VLDL to the VLDL in hepatic lymph through the use of vitamin A labeled VLDL. To further test the validity of using the hepatic lymph cannulated rat as an in vivo model for studying lipoprotein secretion by the liver, we will study the output of apoprotein and lipid in hepatic lymph VLDL when the rats have been treated with a high sucrose diet, alcohol, ethynyl estradiol and 4-aminopyrazolopyrimidine. Lastly, the hepatic lymph cannulated rat will be used to study the effect of intestinal lymph diversion on lipoprotein secretion by the liver. The long-term objectives of this research are the use of this in vivo model to study the factors that regulate the secretion of lipoproteins by the liver and the metabolism of the hepatic lymph lipoproteins.
