De novo synthesis of fatty acid in perfused rat liver as a determinant of plasma lipoprotein production

Abstract

The quantitative relationship between fatty acid synthesis de novo and production of plasma lipoproteins by perfused liver has been investigated. Livers of rats were perfused in situ for 3–5 hours with a suspension of erythrocytes in one of three perfusing media: rat plasma, buffer containing albumin, or a mixture of plasma and buffer. Tritium oxide (2 mC) was added in each case. Livers were from young rats fed adlibitum or fasted and re-fed. Rates of hepatic fatty acid synthesis ranged from 1.4 to 14.1 μmoles/gm liver/hour, as determined from the tritium content of fatty acids in the liver plus perfusate. A high correlation was found between the number of micromoles of fatty acid synthesized by livers and the number of micromoles of esterified fatty acid released by livers into the perfusing medium. When the perfusate was prepared with only plasma, 0.9 mole of total fatty acid was released per mole synthesized. With all perfusing media, net release of triglycerides, and to a lesser extent cholesterol, was highly correlated with rate of fatty acid synthesis. The additional amounts of triglycerides and cholesterol resulting from accelerated fatty acid synthesis were all released into the perfusate β-lipoprotein fraction, identified immunochemically and by ultracentrifugation. Livers with similar rates of fatty acid synthesis released more triglyceride, cholesterol, and newly synthesized fatty acid when the perfusing medium contained plasma. Net release of phospholipids was nearly independent of the rate of fatty acid synthesis or the presence of plasma in the perfusate. The rate of fatty acid synthesis de novo, which varied widely among even carefully selected rats, is an important determinant of lipid release by the perfused liver.