INCREASED PLASMA, BILIARY, AND HEPATIC CHOLESTEROL PRECURSORS IN PIGSWITH ILEAL AUTOTRANSPLANTATION-INDUCED MALABSORPTION OF CHOLESTEROL AND BILE-ACIDS

Background: Small-bowel transplantation impairs intestinal absorptive function for unknown reasons. Methods: The proportions of plasma, bili ary, and hepatic cholesterol precursors to cholesterol were determined by gas-liquid chromatography after resection of the proximal 75% of t he porcine jejunoileum (n = 15) and autotransplantation of the remaini ng ileum (n = 15) and were related to in vivo absorption and fecal exc retion of cholesterol. Results: Ileal autotransplantation significantl y decreased serum (18%; P < 0.05) and liver (7.6%; P < 0.05) cholester ol content, the esterification percentage of serum cholesterol (5.1%; P < 0.0001), and the total amount of cholesterol absorbed (48%; P < 0. 05) and increased fecal excretion of bile acids (108%; P < 0.0001), ne t cholesterol elimination (53%; P < 0.001), and the proportions of pla sma (207%; P < 0.0001), biliary (183%; P < 0.0001), and hepatic (114%; P < 0.0001) cholesterol precursors. The increases were most striking for the side-chain-saturated demethylated sterols, cholestenol and lat hosterol, and monomethyl sterols, whose bile/liver and plasma/liver ra tios were increased in the autotransplantation group. Plasma, biliary, and hepatic precursor proportions were positively related to each oth er and similarly correlated with fecal bile acids and the net eliminat ion of cholesterol in feces. Conclusions: These findings suggest that ileal autotransplantation in pigs with proximal gut resection increase d the levels of cholesterol precursor sterols in plasma, bile, and liv er mainly due to a bile-acid-malabsorption-induced increase in hepatic synthesis of cholesterol. Enhanced secretion of cholesterol precursor s from the liver into the plasma and bile may have contributed to thei r increased values during the increased rate of cholesterogenesis.