出版社：American Society for Biochemistry and Molecular Biology
摘要：Chenodeoxycholic acid (CDCA), in contrast to cholic acid (CA), reduces cholesterol saturation of bile. The mechanisms for these differences were the object of this study. Investigations were carried out in nine white men; three nonobese subjects and one obese subject were fed a weight-maintenance diet, and five obese patients had a reduced caloric intake for weight reduction. They were given a daily dose of 750-1000 mg CDCA or CA for one month after which they received the other bile acid for another month. The effects of both bile acids on bile acid pool size and hepatic secretion rates of biliary lipids were determined. Total bile acid pools were increased markedly by both CDCA and CA, but to about the same degree for each. Thus, the superior action of CDCA for lowering saturation of bile could not be explained by its effect on the pool sizes of bile acids. On the other hand, hepatic secretion of cholesterol, both during feeding and fasting, was found to be reduced to a greater extent by CDCA than by CA. A theoretical mechanism by which CDCA might lower hepatic outputs of cholesterol is the inhibition of cholesterol absorption. To examine this possibility, cholesterol absorption was estimated by use of an intestinal perfusion technique. No differences were obtained between the two treatment periods for either percentage or net absorption of cholesterol; thus it is unlikely that decreased absorption could account for the reduced cholesterol secretion. Another possibility is that CDCA might affect the interrelations of the three biliary lipids differently than CA. This was explored by measurements of hepatic secretion rates of these lipids. We observed a linear relationship between the secretion rates of bile acids and cholesterol, cholesterol and phospholipids, and bile acids during both treatment periods. However, cholesterol:phospholipid ratios were higher during CA therapy than with CDCA, and they increased still more during fasting in most CA-treated subjects, but not with CDCA. This indicated that there is a marked difference between the two bile acids in the degree of coupling of cholesterol and phospholipids in fasting. We suggest that the reduction in bile sa;uration on CDCA is most likely the result of changes in the interrelations of the different biliary lipids at the site of their secretion and/or inhibition of cholesterol output from the liver because of suppressed cholesterol synthesis in this organ.
