results show that bile acids strongly interfere with the The existence of a relationship between bile acid and assembly or secretion of VLDL particles by human hepatriacylglycerol metabolism in humans has been estabtocytes, suggesting a physiological function of the enlished, but the underlying mechanism and its physiologiterohepatic circulation of bile acids in the regulation of cal relevance have remained unclear. We have studied postprandial serum lipid levels. (HEPATOLOGY 1996; the effects of bile acids on the secretion of very-low-den-23:218-228.) sity lipoprotein (VLDL)-associated triacylglycerol, using [ 3 H]glycerol labeling technique, and apolipoprotein B (apoB) in human hepatocytes in primary culture. Hu-Hepatocytes secrete substantial amounts of lipids at man hepatocytes secrete nascent VLDL with an average their apical (canalicular) pole into bile and at the basodiameter of about 40 nm. Lipid composition of the partilateral (sinusoidal) side into the blood, the latter cles resembles that reported for plasma VLDL, with the mainly in the form of very-low-density lipoprotein exception of a markedly lower cholesterylester content. (VLDL). The apical route, i.e., the flux of free choles-In 24-hour cultured human hepatocytes, physiological terol (CH) and phospholipids (PL) into the bile, is (i.e., portal) concentrations of taurocholic acid (10 to 200 thought to occur mainly through vesicle formation at mmol/L) suppressed [ 3 H]triacylglycerol secretion dose dependently. The degree of inhibition highly correlated the canalicular membrane in a process under control of (r Å .87, P õ .01) with taurocholic acid content of the intracanalicular bile acids and mdr2 P-glycoprotein. 1,2 cells of different preparations (n Å 7). ApoB secretion VLDL secretion involves the packing of triacylglycerol was inhibited by taurocholic acid to a similar extent as (TG), cholesteryl ester (CHE), CH, and PL together [ 3 H]triacylglycerol secretion (r Å .93, P õ .01). Lipid com-with apolipoprotein (apo) B into nascent VLDL in the position of secreted VLDL particles did not change durendoplasmic reticulum, processing of the particles in ing taurocholic acid-induced suppression. No effects on the Golgi complex, and secretion through an exocytotic intracellular apoB, [ 3 H]triacylglycerol, triacylglycerol, pathway. 3,4 In spite of the different nature of both seand cholesterol mass were observed, nor did taurocholic cretory processes, they appear to be connected in a acid affect protein synthesis, albumin secretion, or lacfunctional sense. In animals, dietary and pharmacologtate dehydrogenase (LDH) release. Cellular cholesteryl ester (CHE) mass, however, was markedly reduced. Our ical manipulations that increase or decrease biliary CH secretion generally have an opposite effect on serum CH and TG levels and VLDL production.
5-7 Interactions of bile acids with both secretory processes have been Abbreviations: VLDL, very-low-density lipoprotein; CH, cholesterol; PL, phospholipids; TG, triacylglycerol; CHE, cholesterol ester; apoB, apolipopro-reported. The stimulatory effects of bile acids on biliary tein B; FCS, fetal calf serum; BSA, bovine serum albumin; HBSS, Hank's lipid secretion in various experimental models as well balanced salt solution; OA, oleic acid; PBS, phosphate-buffered saline; LDH, as in humans are well established. 1 Likewise, a relalactate dehydrogenase; cAMP, cyclic adenosine monophosphate.
tionship between bile acid metabolism and VLDL pro-From the Departments of 1 Pediatrics,