Resistant starch and cholestyramine have distinct effects on hepatic cholesterol metabolism in guinea pigs fed a hypercholesterolemic diet

Abstract

The effects of resistant starch (RS) and cholestyramine (CHY) on cholesterol metabolism were tested in guinea pigs. Animals were fed cellulose ( 14 g 100 g ) (control diet) RS ( 10 g 100g ) or CHY ( 1 g 100 g ) for a period of 4 weeks. All diets contained 19 g 100 g fat, 0.17 g 100 g cholesterol and 36 g 100 g carbohydrate with sucrose contributing 80% to the carbohydrate energy. Guinea pigs fed RS and those treated with CHY had 27% and 75% lower plasma cholesterol concentrations than the control group (P< 0.01) while plasma triacylglycerol levels did not differ. The hypocholesterolemic effects of RS and CHY were associated with the LDL fraction while no changes in plasma VLDL or HDL cholesterol concentrations were observed. In addition, guinea pigs from the RS group exhibited an LDL particle with lower number of triacylglycerol molecules compared to LDL from controls (P < 0.01). Hepatic free, esterified cholesterol and triacylglycerol were 37 to 60% lower in guinea pigs fed RS and in those treated with CHY compared to the control group (P < 0.01). Hepatic HMG-CoA reductase activity was 6- and 36-fold higher in guinea pigs fed RS and treated with CHY compared to control animals (P < 0.01); ACAT activity was 50% lower in both RS and CHY groups compared to the control group and only guinea pigs treated with CHY exhibited a 4-fold increase in cholesterol 7α-hydroxylase activity compared to controls. The data from these studies suggest that although both RS and cholestyramine lower plasma LDL cholesterol concentrations, the order of magnitude is different, and the distinct effects of these two treatments on hepatic cholesterol homeostasis suggest that different mechanisms are involved in the plasma cholesterol lowering.