DIETARY TRIGLYCERIDES AND PLASMA-BILIARY LIPID BALANCE

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Elevations in serum cholesterol (CHL) are causally related to an increased incidence of atherosclerosis and coronary heart disease. Dietary poly-unsaturated fats have received a great deal of attention for their ability to decrease levels of serum CHL and triglycerides (TG). Studies suggest that the reduction in serum CHL is due at least in part to an increased secretion of CHL into bile, and this could lead to an increased incidence of CHL gallstones. Recent studies in the paired dog suggest that dietary omega-6 polyunsaturated fatty acids do in fact accelerate gallstone formation, but dietary supplementation with omega-3 fatty acids actually decreases the incidence of gallstones. Furthermore, there has been some suggestion that modification of biliary lipids by diet may influence CHL transport and solubility in bile. The hypotheses to be tested are that 1) dietary polyunsaturated fats reduce serum CHL in part by enhancing biliary CHL secretion and 2) dietary TGs may alter the CHL-carrying capacity of bile by altering the molecular species, total concentrations, and/or secretion rates of biliary lipids. The aim of this study is to examine the effect of modifying both the type and amount of dietary TG and CHL on: 1) The balance of lipids between plasma and bile. Lipid concentrations will be measured in plasma lipoproteins and whole plasma, and lipid concentrations and secretion rates will be measured in bile. Alterations in the two compartments will be correlated. 2) The CHL-carrying capacity of bile. Biliary vesicles and mixed micelles will be separated, and alterations in lipid composition of the particles as well as changes in the incidence of CHL monohydrate crystals in bile will be noted. 3) The central role of the liver in maintaining the lipid balance between plasma and bile. Levels of hepatic lipids will be compared to the levels of the corresponding lipids in plasma and bile. The hepatic enzymes of CHL metabolism will be assayed (acyl CoA-CHL acyl transferase, HMG CoA reductase, and CHL 7-alpha hydroxylase), and Northern blot hybridization will be used to quantitate the levels of hepatic mRNA for the last two enzymes.