Fractionation of livers following diosgenin treatment to elevate biliary cholesterol

The plant saponin, diosgenin, is known to induce a marked increase in biliary cholesterol/phospholipid ratio. We reasoned that putative biliary lipid supply vesicles might be similarly enriched with cholesterol. Seven-day diosgenin feeding to rats resulted in significantly increased biliary cholesterol and cholesterol/phospholipid ratio, but had no effect on total cholesterol or phospholipid content of the liver. Subcellular fractionation of livers showed no selective increase in any fraction (nuclear, mitochondrial, lysosomal, microsomal) of the homogenate. Further subfractionation of microsomal or nuclear (plasma membrane) fractions also showed no difference between control and diosgenin groups. Thus, no intracellular vesicle fraction has been identified with the provision of the enhanced biliary cholesterol and the results are discussed in terms of the possible involvement of cytosolic lipid-binding proteins as putative lipid carriers to the canalicular membrane as an alternative to the presence of the lipid in lipid supply vesicles.