Cholesterol homeostasis in guinea pigs fed saturated and polyunsaturated fat diets

Whole body sterol balance, hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity, hepatic low-density lipoprotein (LDL) receptor levels and net tissue cholesterol concentrations were determined in guinea pigs fed either a corn oil- or lard-based purified diet for 6-7 weeks. In comparison to the saturated lard diet, the polyunsaturated corn oil diet resulted in a 34% reduction in plasma total cholesterol levels (P less than 0.02) and a 40% lower triacylglycerol level (P less than 0.02). Feeding the corn oil diet altered very-low-density lipoprotein (VLDL) and LDL composition; the percent cholesterol ester in both particles was decreased and the relative percentages of VLDL triacylglycerol and LDL phospholipid increased. The ratio of surface to core components of LDL from corn oil-fed guinea pigs was significantly higher compared to LDL from animals fed lard. Dietary fat quality had no effect on fecal neutral or acidic steroid excretion, net tissue accumulation of cholesterol, whole body cholesterol synthesis or gallbladder bile composition. Consistent with these results was the finding that fat quality did not alter either expressed (non-phosphorylated) or total hepatic HMG-CoA reductase activities. The hepatic concentrations of free and esterified cholesterol were significantly increased in corn oil-fed animals, as were cholesterol concentrations in intestine, adipose tissue, muscle and total carcass. Analysis of receptor-mediated LDL binding to isolated hepatic membranes demonstrated that the polyunsaturated corn-oil based diet caused a 1.9-fold increase in receptor levels (P less than 0.02). The data indicate that the hypocholesterolemic effects of dietary polyunsaturated fat in the guinea pig are not attributable to changes in endogenous cholesterol synthesis or catabolism but rather may result from a redistribution of plasma cholesterol to body tissue due to an increase in tissue LDL receptors.