Interactive effects of dietary fat type and cholesterol quantity on cholesterol and lipoprotein metabolism in the guinea pig.

Abstract

Cholesterol and lipoprotein metabolic regulation by dietary fat and cholesterol was studied in guinea pigs fed 15% fat (w/w) diets differing in fat saturation (saturated lard, monounsaturated olive oil, or polyunsaturated corn oil) and cholesterol amount (Basal (0.01%), Low (0.08%), Medium (0.17%), or High (0.33%)). Absorbed cholesterol intakes provided 6, 50, 100, and 200% respectively the mass of endogenous cholesterol synthesis. Dietary fat and cholesterol interactions affected plasma lipoprotein cholesterol concentrations, hepatic LDL binding, LDL composition, and hepatic free and esterified cholesterol levels. Hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity was independently suppressed by olive-oil based diets and cholesterol intakes above Basal levels, reflecting the regulation of cholesterol biosynthesis by hepatic cholesterol levels. Cholesterol-mediated down-regulation of hepatic LDL receptors correlated with plasma LDL levels, consistent with the primary role of the receptor in LDL uptake. In general, regulatory effects of fat type was more prominent with moderate cholesterol intakes, and diets containing lard or olive oil were hypercholesterolemic as compared to corn oil. Homeostatic regulatory mechanisms maintained plasma total and LDL cholesterol concentrations within modest ranges with moderate cholesterol intakes; however, High cholesterol intake resulted in large increments in plasma total and LDL cholesterol levels. Plasma HDL cholesterol concentrations were interactively increased by dietary cholesterol and fat type, although the changes were modest. HDL apo A-I fractional catabolic rates were not altered by dietary treatment and specific hepatic HDL binding did not constitute a significant catabolic route. Dietary cholesterol affected apo A-I mRNA levels in a tissue-specific manner such that intestinal apo A-I mRNA levels did not change but hepatic levels were increased; however, apo A-I mRNA abundance did not correlate with plasma HDL cholesterol concentrations, suggesting that post-transcriptional events may be more important determinants of apo A-I production than transcript abundance. Significant interactions between dietary fat saturation and cholesterol amount were demonstrated to alter regulatory mechanisms which maintain plasma cholesterol homeostasis. Where independent dietary fat and cholesterol effects occurred, cholesterol amount was generally a more significant dietary regulator than fat type.