Dietary fat type and cholesterol quantity interact to affect cholesterol metabolism in guinea pigs

Interactions of dietary fat saturation with dietary cholesterol on cholesterol homeostasis in guinea pigs were studied by feeding 15% (wt/wt) fat diets containing lard, olive oil or corn oil, with 0.00, 0.08, 0.17 or 0.33% added cholesterol. Plasma total and LDL cholesterol concentrations significantly increased with increasing dietary cholesterol, with pronounced increments occurring at the pharmacologic (0.33%) level. An interaction between fat type and dietary cholesterol was seen for HDL cholesterol concentrations. Saturated fat and the pharmacologic level of dietary cholesterol increased plasma HDL concentrations, whereas polyunsaturated fat minimized the dietary cholesterol-mediated increase. Interactions were also observed for hepatic cholesterol: dietary cholesterol increased both free and esterified hepatic cholesterol concentrations in all groups fed all the dietary fats, and fat type influenced the extent of hepatic cholesterol accumulation. Lard-fed animals accumulated the least hepatic cholesterol over the range of dietary cholesterol intakes. Dietary cholesterol suppressed hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity, with maximal suppression at all levels of cholesterol intake. Dietary cholesterol had a greater effect on plasma and hepatic cholesterol concentrations and hepatic HMG-CoA reductase activity than did fat type. The data indicated limited interactions of fat type and cholesterol quantity in altering mechanisms regulating plasma cholesterol homeostasis.