Dietary fatty acids and the regulation of plasma low density lipoprotein cholesterol concentrations

Epidemiologic studies over the past 25 years have shown that the level of dietary fat intake is positively correlated with the average serum cholesterol value and mortality from coronary heart disease (CHD). A number of different investigators demonstrated that in addition to total fat, the fatty acid composition of diets influenced serum total cholesterol (TC) in humans. In general, saturated fatty acids were found to elevate the serum cholesterol concentration, and unsaturated fatty acids were found to decrease this value. The lipoprotein fraction most affected was the level of cholesterol carried in low density lipoprotein (LDL-C). It has now been demonstrated that the steady-state level of LDL-C is predominantly dictated by metabolic events in the liver. As the amount of dietary cholesterol entering the body is increased, there is expansion of the sterol pool in the liver cell and down regulation of LDL receptors (LDLR) that are primarily responsible for clearing LDL-C from the blood stream. When dietary cholesterol intake is kept constant, however, long-chain saturated fatty acids further suppress hepatic LDLR activity, whereas several unsaturated fatty acids have the opposite effect. These regulatory events depend upon the availability of the various fatty acids to shift intracellular cholesterol between a regulatory and storage pool of cholesterol, and this effect is mediated by the enzyme acyl-CoA:cholesterol acyltransferase (ACAT).