Comparative effects of saturated and unsaturated lipids on hepatic lipogenesis and cholesterogenesis in vivo in the meal-fed rat.

The effects of saturated and unsaturated lipids on in vivo rates of hepatic lipogenesis and cholesterogenesis were compared. Lipogenic and cholesterogenic rates were determined in meal-fed rats either after feeding 1%, 5%, 10%, or 20% dietary corn oil or hydrogenated soybean oil for 14 days, or after intrgastric administration of fatty acyl ethyl esters (18:0, 18:1, or 18:2) for 1 and 3 days. Dietary hydrogenated soybean oil was not absorbed, whereas dietary corn oil and the intragastrically administered fatty acyl ethyl esters were well absorbed. Fatty acid synthesis measured from 3H2O and [14C] alanine was inversely correlated with unsaturated dietary fat content, but was unchanged by saturated dietary fat. A single daily administration of 18:0, 18:1, or 18:2 was ineffective in altering lipogenic rates. However, fatty acid synthesis was decreased by three consecutive daily doses of 18:1 or 18:2 (5 g/kg), but not by 18:0. Hepatic rates of cholesterogenesis from 3H2O and [14C] alanine were markedly enhanced by the administration of 10% or 20% saturated dietary fat. Feeding 1%, 5%, or 10% corn oil diets did not have an effect on cholesterogenesis. The 20% corn oil diet reduced the rate of conversion of [14C]anine into cholesterol while the rate of conversion of 3H2O remained unchanged. Neither the 1 day not 3 day oral administration of 18:0 or 18:1 had any effect on cholesterol synthesis; thereas the administration of 18:2 increased the conversion of [14C] alanine into cholesterol by 30% but did not after the rates of cholesterogenesis from 3H2O. These data suggest the following: a) fatty acid synthesis responds selectively to 18:0, 18:1, and 18:2; b) the inhibition of fatty acid synthesis by unsaturated fatty acids is time dependent; c) the rate of fatty acid synthesis is inversely proportional to the concentration of unsaturated dietary fat; d) prolonged feeding with a completely saturated diet will increase fecal fat excretion and hepatic cholesterol synthesis; and e) the regulation of fatty acid synthesis by dietary lipid is independent of the regulation of cholesterol synthesis.