Cerebral low-density lipoprotein (LDL) uptake is stimulated by acute bile drainage.

Although the cholesterol pool in the central nervous system is considered to be relatively stable, few studies have tested this assumption. The aim of the study was to gain further information on the communication between the extracerebral organs and the brain as far as cholesterol and lipoprotein transport are concerned. Receptor-dependent as well as receptor-independent LDL uptake in the brain were measured, by established methods, after constant 1-h intravenous infusions of [14C]sucrose-labelled hamster LDL and methylated human LDL, both in hamsters with an acute bile fistula and in control animals with an intact enterohepatic circulation. The receptor-dependent LDL uptake in the brain promptly showed a significant increase after the construction of the bile fistula. However, there was no difference in the receptor-independent LDL uptake between the bile fistula and control animals. The studies indicate the presence of close communications between extracerebral and brain cholesterol. Changes in the extracerebral compartments of cholesterol are, apparently, readily sensed by the LDL receptor in the brain and promptly evoke appropriate modifications in its activity.

Effects of bile acid depletion and of ursodeoxycholic and chenodeoxycholic acids on biliary protein secretion in the hamster.

The effect of changes of both the rate of secretion and the composition of bile acids on biliary proteins was studied in a bile fistula hamster model. Biliary protein secretion as well as bile flow and bile acid secretion were studied in response to intravenous infusions of low, medium and high doses of ursodeoxycholic acid and chenodeoxycholic acid in comparison to the infusion of the normal saline carrier (control) solution. The control-infused animals showed a marked and statistically significant increase in both the concentration and total excretion of biliary proteins. All three doses of ursodeoxycholic acid either prevented the increase of protein concentration or led to its decrease. The low and medium doses of chenodeoxycholic acid had similar effects. However, the high dose of this bile acid was cholestatic and increased the biliary protein concentration. The results of the study indicate that decreases in bile acid secretion, as they occur after an interruption of the enterohepatic circulation, may lead to major increases in biliary protein concentration. The study also shows that these changes in protein secretion, which may promote nucleation, are reversed by the cholelitholytic bile acids, ursodeoxycholic acid and chenodeoxycholic acid.

Interaction of potentially toxic bile acids with human plasma proteins: binding of lithocholic (3 alpha-hydroxy-5 beta-cholan-24-oic) acid to lipoproteins and albumin.

The binding of lithocholic acid to different plasma fractions was studied. When whole plasma was incubated for 8 hr, approximately 25% of the incubated [14C]lithocholic acid was bound to the lipoprotein and lipoprotein-free, albumin-rich fractions. An average of 87.6% of the bound-lithocholic acid was present in the lipoprotein-free, albumin-rich fraction, 7.2% in high density lipoproteins, 2.2% in low density lipoproteins, 1.0% in intermediate density lipoproteins and 2.0% in very low density lipoproteins. Expressed as binding per microgram protein, considerably less [14C]lithocholic acid was bound to the lipoprotein-free, albumin-rich fraction, than to the lipoproteins. The binding of [14C]lithocholic acid after the incubation of the isolated plasma fractions was similar to that found after the incubation of whole plasma. The highest transfer of [14C]lithocholic acid occurred from the lipoprotein-free, albumin-rich fraction to the lipoprotein fractions. The studies indicate, that, although the largest amount of lithocholic acid is bound to the lipoprotein-free, albumin-rich fraction, per microgram protein, the binding of lithocholic acid to lipoproteins is more pronounced and stable than that bound to the lipoprotein-free, albumin-rich fraction. Since lipoproteins, in contrast to albumin, are internalized by most tissues, they may be important carriers into cells of lithocholic acid and other potentially toxic or tumorigenic bile acids.

Fecal bile acid excretion and composition in response to changes in dietary wheat bran, fat and calcium in the rat.

The effect and possible interactive influence of different dietary amounts of wheat bran, fat and calcium on the fecal excretion, concentration and composition of bile acids was studied in Fischer-344 rats. The fecal bile acids were analyzed using gas-liquid chromatography. Dietary wheat bran increased both total bile acid excretion and fecal weight without changes in fecal bile acid concentration. The proportion of fecal hyodeoxycholic acid decreased with increasing dietary fiber, whereas that of lithocholic and deoxycholic acids increased significantly with fiber intake. The percent content of fecal chenodeoxycholic acid did not change. Increasing dietary fat led to an increase in bile acid excretion without changes in either fecal weight or bile acid concentration. In contrast, the level of dietary calcium did not affect the total excretion of bile acids. However, since calcium increased the fecal weight, it consequently diluted bile acids and decreased their fecal concentration. Dietary fat and calcium had no influence on fecal bile acid composition. There were no interactive effects of wheat bran, fat and calcium on fecal bile acids. The finding in this study that dietary fiber, fat and calcium induce significant changes in fecal bile acids may be of relevance to the potential of bile acids to promote carcinogenesis.