Hepatic lipid metabolism in experimental diabetes. V. The effect of concentration of oleate on metabolism of triglycerides and on ketogenesis.

1. Livers from normal and alloxan diabetic rats were perfused in vitro with a medium in which the concentration of free fatty acid was maintained at relatively constant levels by the infusion of a complex of oleic acid and bovine serum albumin. Concentrations of free fatty acid up to 3.5 mM in the cell-free perfusate were attained. 2. Throughout the range of concentration of free fatty acid which might be expected in the blood under normal and pathological conditions in vivo, the uptake of free fatty acid by the liver in vitro was proportional to the concentration in the medium; rates of uptake of free fatty acid approached saturation only at concentrations of free fatty acid in excess of those encountered in vivo. 3. The accumulation of triglyceride in livers from normal and most probably also in livers from alloxan diabetic rats was proportional to the concentration of free fatty acid in the medium. In contrast to triglyceride, the concentrations of total phospholipid, cholesterol, cholesteryl esters, and free fatty acid in the livers from normal and alloxan diabetic animals was independent of the concentration of free fatty acid in the perfusate. 4. Ketogenesis by livers from normal rats was dependent on the concentration of oleate in the medium; the maximal rates of production of ketone bodies were observed at 1.7 mu oleate. The rate of ketogenesis by livers from normal rats never equaled that by livers from alloxan diabetic animals, regardless of the concentration of free fatty acid in the medium. Although ketogenesis by livers from diabetic rats was responsive to the presence of oleate in the medium,