It has been proved that the viscosity associated with dietary soluble polysaccharides interferes with cholesterol absorption by directly binding cholesterol within the intestine, interfering with the diffusion of cholesterol toward the epithelial cell surface. We thus propose the reduction of cholesterol absorption in response to APS maybe attributed to its viscosity, with little regulation of genes associated with cholesterol transport. Cholesterol is mainly eliminated from the body via conversion to bile acids, and the rate-limiting enzyme of the process is cyp7a1. It has been reported that dietary soluble polysaccharides decreased serum cholesterol by altering the composition of the enterohepatic bile acid pool and increasing the fecal loss of total bile acids. In response to increased fecal bile acid excretion, there occurs a compensatory LY2109761 increase in bile acid synthesis. In this study, we reported for the first time that APS produced a marked increase in excretion of fecal bile acids, in accordance with our observations that the hepatic cyp7a-1 mRNA expression was significantly elevated in response to APS. A further test with Western blotting also revealed that the APS stimulated cyp7a-1 protein expression. The effect on bile acid metabolism would support the conclusion that APS lowers blood cholesterol partly by increasing bile acid excretion. However, additional studies are required to further investigate the mechanism by which APS inhibits cholesterol absorption and increases bile acid excretion. Increased cholesterol synthesis by cholesterol absorption inhibitors has been reported in many previous studies. We observed for the first time that APS also increased cholesterol synthesis, different from that of statins. Cholesterol synthesis increases reciprocally to the reduction of absorption as a compensatory metabolic response, as indicated by an increase in the fecal excretion of neutral sterols and liver HMGCoA reductase activity in our study. It can be speculated that the increase in cholesterol synthesis is mainly due to de novo hepatic cholesterol. Although the reciprocal increase of cholesterol synthesis might have compromised partly the cholesterol lowering efficacy of the treatments, our data and many previous reports demonstrated plasma cholesterol was still significantly reduced. The results suggest that supplementation of APS for 3 months may be beneficial to liver health and function, which is supported by a significant decrease of ALT and AST and amelioration of liver fatty degeneration in hamsters under the experimental conditions. The expression of liver LDLR regulates plasma LDL-C homeostasis in both human and hamsters. Increased hepatic LDLR expression results in improved clearance of plasma LDL-C through receptor-mediated endocytosis. The activation of LDLR gene expression through depletion of intracellular cholesterol is the principal working mechanism of statins. In this study, we demonstrated that APS had strong activities in stimulating hepatic LDLR mRNA expression.