Weight loss associated with tumor burden has been postulated to be due to an energy imbalance resulting from increased hepatic gluconeogenesis secondary to Cori cycle activity. The mechanisms which control pyruvate metabolism are inherent to the control of gluconeogenesis in the liver. Therefore, the metabolism of pyruvate was evaluated in a transplanted tumor model in rodents which has previously shown an increased rate of hepatic gluconeogenesis. Female Lewis-Wistar rats received a s.c. injection of a suspension of mammary tumor cells in the left flank. Tumor-bearing rats were allowed ad libitum food consumption, and non-tumor-bearing controls were pair-fed to the consumption of their tumor-bearing cohorts. At Days 12, 13, and 14 following inoculation, tumor-bearing and non-tumor-bearing controls were used for in vivo body composition analysis or subjected to isolated liver perfusion. Animals were not fasted prior to sacrifice. Pyruvate use by the livers of tumor-bearing and pair-fed non-tumor-bearing rats was evaluated in the presence of 8 mm glucose and 5 mw lactate. Pyruvate clearance was increased by 270%, and pyruvate intake was increased by 212% compared to pair-fed non-tumor-bearing rats. Oxidation of pyruvate to CO2 was increased 130%, and pyruvate conversion to lactate was increased by 197% above that seen in pair-fed nontumor-bearing rats. Gluconeogenesis from pyruvate was in creased by 184% in tumor-bearing rats.

The increased gluconeogenesis in tumor-bearing rats above that of control animals at a 5 mw lactate concentration suggests that some factor, other than substrate supply, may stimulate gluconeogenesis in tumor-bearing rats. Although the use of pyruvate was greater in tumor-bearing rats, the disposal of pyruvate carbon into CO2, lactate, and glucose was proportionally the same in both groups. Therefore, these data suggest that the increased metabolism of pyruvate in tumor-bearing rats is controlled by a mechanism affecting cellular pyruvate transport.


This research is supported in part by Grant CA 16520-07 from the National Cancer Institute, Veterans Administration Medical Research funds, and departmental funds from the Rhode Island Hospital.

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