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Journal of Lipid Research, Vol. 4, 461-469, October 1963
Copyright © 1963 by Lipid Research, Inc.

Fate of palmitate and of linoleate perfused through the isolated rat liver at high concentrations

Paul J. Nestel and Daniel Steinberg

Laboratory of Metabolism, National Heart Institute, National Institutes of Health, Bethesda 14, Maryland

When rat livers were perfused with red cell-albumin solutions containing high concentrations of free fatty acids (FFA), the FFA were very rapidly taken up. Concomitantly, the glyceride content of the liver rose by 25-60% over control values, the absolute increment corresponding roughly to the amount of FFA taken up. The net increase in liver glyceride content was independent of whether palmitate, linoleate, or a combination of the two was used to raise the FFA concentration of the perfusate. The results support the conclusion drawn from earlier in vivo studies that high serum FFA levels can directly contribute to development of fatty liver. When the initial FFA concentration of perfusate was less than 1 µEq/ml, there was no significant increment in the glyceride content of the perfusate. When the initial FFA concentration of the perfusate was high (2-3 µEq/ml), the glyceride content of the perfusate rose significantly during a 90-min perfusion. The changes in the fatty acid pattern of the glycerides in the liver and in the perfusate indicated that the fatty acid added to the perfusate to raise the FFA concentration to high levels was being preferentially utilized for formation of the new glycerides, but the quantitative effects when perfusing with palmitate alone and linoleate alone differed. Perfusion with palmitate markedly increased the percentage of palmitate in liver glycerides but increased only slightly the percentage of palmitate in the perfusate glycerides. Linoleate had less effect on the fatty acid pattern of the liver glycerides and a greater effect on that of the perfusate glycerides. The differences between the metabolic fates of the two fatty acids are consistent with results of in vivo studies reported previously. Studies of utilization of labeled FFA by liver slices showed that relatively more labeled palmitate was incorporated into glycerides and relatively more linoleate into phospholipids. Incorporation into other lipids and conversion to CO₂ were also compared. Livers were perfused with palmitate at low and at high concentration adding palmitate-1-C¹⁴ as a tracer. It was shown that high FFA concentrations strongly stimulated conversion to C¹⁴O₂ and incorporation into glycerides but had a less marked effect on incorporation into phospholipids.

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