INTRAHEPATIC BILIARY CHOLESTEROL AND PHOSPHOLIPID TRANSPORT IN HUMANS- EFFECT OF OBESITY AND CHOLESTEROL CHOLELITHIASIS

The mode of transport of biliary lipids within the hepatocyte and the role of the bile canalicular membrane (BCM) in biliary lipid secretion are not well understood. We hypothesized that biliary cholesterol and phospholipid are co-transported across the hepatocyte in vesicular fo rm from the endoplasmic reticulum to the bile across the BCM. We obtai ned wedge liver biopsies and fasting gallbladder bile from 15 choleste rol gallstone patients and 10 control subjects. BCM, basolateral membr ane (BLM), and many microsomal vesicular fractions were isolated by ce ntrifugation. One of the vesicular fractions (V3) was enriched in both the microsomal and the BCM marker enzymes and had a high phosphatidyl choline proportion in its phospholipid with a fatty acid pattern simil ar to biliary phosphatidylcholine. Moreover, its cholesterol content w as increased in the obese cholesterol gallstone subjects, who had an i ncrease in cholesterol synthesis, as indicated by the increased activi ty of the HMG-CoA reductase. The cholesterol content correlated with H MG-CoA reductase activity. A direct correlation was found between chol esterol/phospholipid ratio in V3, BCM, and in bile but not in the BLM. These data are in agreement with the assumption that this vesicular f raction is involved in the transport of cholesterol and phospholipid f rom the endoplasmic reticulum to the site of secretion in the BCM, and thence to bile, and that this transport is enhanced in obese gallston e patients.