Regulation of energy metabolism in Morris hepatoma 7777 and 7800.
The pathway of fat oxidation in two experimental hepatomas was studied in order to demonstrate that a specific deficit in the energy metabolism of a tumor might contribute to the cachexia of the host. Forty-eight male Buffalo rats were divided into four groups of 12 each. One group was implanted s.c. with Morris hepatoma 7777 and one group was implanted with Morris hepatoma 7800, whereas the other two groups served as controls. All groups were fed standard rat chow diet ad libitum until the tumors reached 2 cm in diameter. The animals were then fasted for 24 hr prior to sacrifice and excision of tumor and liver for assays. During the period of tumor growth, the animals bearing the 7777 hepatoma lost weight, but the weight of the 7800 hepatoma-bearing rats did not differ significantly from that of the control animals. The livers of both groups of animals showed evidence of fatty acid oxidation in vivo and in vitro, and, as expected, during fasting, pyruvate dehydrogenase was inactivated and the rate of fatty acid synthesis was low. A qualitatively similar picture was seen with the better-differentiated 7800 hepatoma. In contrast, the 7777 hepatoma exhibited low levels of fatty acyl coenzyme CoA, no appreciable activity of carnitine palmitoyl transferase and fortified homogenates of the tumor were unable to oxidize palmitate. In keeping with these observations, pyruvate dehydrogenase remained in the active form, and fatty acid synthesis continued unabated in the fasted state in these tumors. Ketone bodies could not be oxidized by fortified homogenates of the liver or by either tumor, probably due to the lack of 3-ketoacid thiotransferase, which was undetectable in these tissues. We hypothesize that flow-through pyruvate dehydrogenase during fasting in Morris hepatoma 7777, occurring as a result of the defect in fat oxidation, contributes to the weight loss of these animals.
D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D002460:Cell Line; D004734:Energy Metabolism; D005215:Fasting; D005227:Fatty Acids / Q000378:metabolism; D007657:Ketone Bodies / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009368:Neoplasm Transplantation; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D051381:Rats
D000214:Acyl Coenzyme A; D005227:Fatty Acids; D007657:Ketone Bodies; D011768:Pyruvate Dehydrogenase Complex