Leucine metabolism in partially hepatectomized rats

We hypothesized that the decrease in plasma branched-chain amino acids (i.e. valine, leucine and isoleucine) and the increase in the oxidized leucine fraction demonstrated in cirrhotic rats in our previous study were caused by the reduced liver cell mass. In the present study we have evaluated the influence of the loss of a substantial amount of the hepatic tissue on changes in leucine metabolism.

A two-thirds partial hepatectomy (PH) was performed in male Wistar rats, weighing 210-250 g. Sham-operated rats served as controls. Whole-body leucine kinetics and ketoisocaproate oxidation rates in the isolated perfused liver were investigated using continuous infusion of [1-14C]leucine and alpha-keto[1-14C]ketoisocaproate at 0 h, 24 h and 72 h after surgery. All groups were compared by analysis of variance, and differences were considered significant at the p < 0.05 level.

A significant decrease in the sum of branched-chain amino acids in blood plasma was observed at 24 h after PH. The decrease in whole-body leucine utilization in protein synthesis observed at 24 h after PH was associated with a decrease in protein synthesis in the gastrocnemius muscle, in the small intestine and in the liver remnant (although protein synthesis per mg of liver protein was higher than in sham-treated animals). In contrast, the rate of whole-body leucine oxidation increased immediately after PH (PH: 4.5 +/- 0.7 vs. sham: 2.4 +/- 0.4; mumol .100 g b.w.-1.h-1). As a result of the opposite changes in protein synthesis and leucine oxidation, marked increases in oxidized leucine fraction were observed immediately (14.6 +/- 1.5%) and 24 h (15.1 +/- 1.6%) after PH in comparison to the sham-treated rats (7.1 +/- 0.8%). In isolated perfused livers of PH rats, an increase in ketoisocaproate oxidation per liver weight unit was observed at 24 h and 72 h in comparison to the sham group. The loss of liver capacity for ketoisocaproate oxidation was restored at 72 h after PH, although the liver weight did not reach the preoperative value.

We conclude that the loss of hepatic tissue results in an increase in leucine oxidized fraction that is caused by both a decrease in protein synthesis and an increase in leucine oxidation. Both the liver remnant and the extrahepatic tissues are involved in this response.