Dietary saturated triacylglycerols suppress hepatic low density lipoprotein receptor activity in the hamster

The liver plays a key role in the regulation of circulating levels of low density lipoproteins (LDL) because it is both the site for the production of and the major organ for the degradation of this class of lipoproteins. In this study, the effects of feeding polyunsaturated or saturated triacylglycerols on receptor-dependent and receptor-independent hepatic LDL uptake were measured in vivo in the hamster. In control animals, receptor-dependent LDL transport manifested an apparent K(m) value of 85 mg/dl (plasma LDL-cholesterol concentration) and reached a maximum transport velocity of 131 μg of LDL-cholesterol/hr per g, whereas receptor-independent uptake increased as a linear function of plasma LDL levels. Thus, at normal plasma LDL-cholesterol concentrations, the hepatic clearance rate of LDL equaled 120 and 9 μl/hr per g by receptor-dependent and receptor-independent mechanisms, respectively. As the plasma LDL-cholesterol was increased, the receptor-dependent (but not the receptor-independent) component declined. When cholesterol (0.12%) alone or in combination with polyunsaturated triacylglycerols was fed for 30 days, receptor-dependent clearance was reduced to 36-42 μl/hr per g, whereas feeding of cholesterol plus saturated triacylglycerols essentially abolished receptor-dependent LDL uptake (5 μl/hr per g). When compared to the approximate kinetic curves, these findings indicated that receptor-mediated LDL transport was suppressed ~30% by cholesterol feeding alone and this was unaffected by the addition of polyunsaturated triacylglycerols to the diet. In contrast, receptor-dependent uptake was suppressed ~90% by the intake of saturated triacylglycerols. As compared to polyunsaturated triacylglycerols, the intake of saturated lipids was also associated with significantly higher plasma LDL-cholesterol concentrations and lower levels of cholesteryl esters in the liver.