Different dietary factors significantly affect cholesterol metabolism and the incidence of cholelithiasis in man. The role of these dietary variations on the mechanism of gallstone induction is not completely understood. The purpose of this application is to systematically study the effects of dietary carbohydrates, proteins and fats (in terms of both nature and concentration) on the following parameters: (a) various aspects of cholesterol/bile acid metabolism (absorption of cholesterol, fecal neutral and acidic steroid output, cholesterol balance, hepatic HMG-CoA reductase and cholesterol 7Alpha-hydroxylase activities and biliary lipids); (b) composition of plasma lipoproteins with regard to apoproteins and lipids; (c) interaction of plasma lipoproteins with hepatic membrane receptors; (d) turnover of plasma lipoproteins. These studies will be carried out in two different hamster gallstone models because of their resemblance to different aspects of human gallstone disease. Once the role of various dietary factors on cholelithiasis has been established it is proposed to study the effect of various bile acids, particularly the """"""""hydrophilic"""""""" cholanoic acids, and bile acid analogs on gallstone prevention and dissolution. The effect of these bile acids on various parameters of cholesterol and lipoprotein metabolism will be studied in the hamster to obtain additional information on their mechanism of action. This study will determine the effect of the hydrophilic bile acids on plasma lipoproteins to evaluate if any of these bile acids may potentially affect the development of atherosclerosis by significantly increasing the levels of plasma LDL. The bile acids and bile acid analogs to be studied include ursodeoxycholic acid, hyodeoxycholic acid, 3Alpha, 6Beta-dihydroxy-5 Beta-cholanoic acid, hyocholic acid, 6-methyl or 7-methyl substituted lithocholic acid, chenodeoxycholic acid, ursodeoxycholic acid and hyodeoxycholic acid.
