DIETARY FATTY-ACIDS REGULATE HEPATIC LOW-DENSITY-LIPOPROTEIN (LDL) TRANSPORT BY ALTERING LDL RECEPTOR PROTEIN AND MESSENGER-RNA LEVELS

The concentration of LDL in plasma is strongly influenced by the amoun t and the type of lipid in the diet. Recent studies in the hamster hav e shown that dietary fatty acids differentially affect circulating LDL levels primarily by altering receptor-dependent LDL uptake in the liv er. To investigate the mechanistic basis of this effect, rates of rece ptor-dependent LDL transport in the liver were correlated with LDL rec eptor protein and mRNA levels in hamsters fed safflower oil or coconut oil and varying amounts of cholesterol. Hepatic LDL receptor activity was significantly lower in animals fed coconut oil than in animals fe d safflower oil at all levels of cholesterol intake (26, 53, and 61% l ower at cholesterol intakes of 0, 0.06, and 0.12%, respectively). Thes e fatty acid-induced changes in hepatic LDL receptor activity were acc ompanied by parallel changes in hepatic LDL receptor protein and mRNA levels, suggesting that dietary fatty acids regulate the LDL receptor pathway largely at the mRNA level.