S Passi

Free fatty acids: a stimulus for mucin hypersecretion in cholesterol gallstone biles

The concentration of free fatty acids, phosphatidylcholine and lysophosphatidylcholine, and the fatty acid composition as well as the levels of the mucins, analyzed by an improved GLC method, were examined in ten biles from patients with cholesterol gallstones (pathological biles) and in ten control biles. In pathological biles the amounts of free fatty acids and phosphatidylcholine, were significantly higher (8.99 +/- 1.09) vs. 2.75 +/- 0.62 micrograms/mg) and lower (6.62 +/- 0.71 vs. 21.91 +/- 3.86 micrograms/mg), respectively, than in control biles, indicating that a relationship exists between the two lipid fractions. Lysophosphatidylcholine concentrations remained unchanged in the two groups (1.02 +/- 0.55 micrograms/mg in pathological biles vs. 1.32 +/- 0.57 micrograms/mg in control biles). The increased levels of free fatty acids were directly correlated (r = 0.73, P less than 0.05) with biliary hypersecretion of mucus glycoproteins. Acetylglucosamine and acetylgalactosamine were significantly higher in pathological biles than in control biles (1.91 +/- 0.67 vs. 0.60 +/- 0.13 microgram/mg). The nucleating potency of the increased amounts of mucins, coupled with lowered levels of phosphatidylcholine, might play a very important role in stone formation and precipitation.

The possible role of free fatty acids in the pathogenesis of cholesterol gallstones in man

The lipid composition of hepatic and gallbladder bile was examined in 20 patients with cholesterol gallstones and in 20 control subjects. Lipid fractions other than bile salts, phospholipids and cholesterol were found to be present, i.e., sterol esters, non-identified fractions and, above all, free fatty acids. The latter probably originated from biliary phospholipids via activity of phospholipases, present in the gallbladder wall. No significant difference in amount and pattern of free fatty acids and phospholipids was found in hepatic bile between patients with gallstones and controls. On the contrary, we observed relevant differences in the lipid composition of gallbladder bile. In this way, we consider that the bile becomes lithogenic inside the gallbladder as a consequence of release of free fatty acids, particularly if these are constituted by saturated chains. In fact, these can compete with cholesterol in the solubilization in biliary micelles. On the other hand, free fatty acids can be directly toxic for the gallbladder wall and produce a cholecystitis.

Analysis of conjugated bile acids by high performance liquid chromatography and mass spectrometry.

Because of the known advantages of coupling high performance liquid chromatography with mass spectrometry (HPLC-MS) in biological fluids, studies on the reversed-phase HPLC-MS system for direct analysis of conjugated bile acids in human bile samples are described. Ten samples of gallbladder bile of apparently healthy subjects were examined. The amounts of each tauro- and glycoconjugated bile acid as trifluoracetate were determined by mass fragmentography. Quantitation of at least 1 ng of each bile acid was possible.

Bile acid content of gallbladder bile and stones in type lib and IV hyperlipoproteinemia

We examined the bile acid composition of gallbladder bile using reversed-phase high performance liquid chromatography (HPLC), in normolipemic and hyperlipidemic (types IIb and IV) patients with cholelithiasis and compared them with normal subjects. Similarly, bile acid composition was determined n the gallstones of these patients. No free bile acids were found in any of the samples examined. We observed that gallbladder bile and gallstones of patients with type IV hyperlipidemia showed a significant increase in the percentage of glyco-conjugated bile acids and reduction in taurine conjugates. Based on this finding we postulate that in addition to biliary lipid composition bile acid composition may also play a role in the pathogenesis of cholesterol gallstone formation.