Some postulates of a hypothesis concerned with the deregulation of muscle turnover by the hypoketonemia of cachectic
tumor-bearing rats were examined. Plasma concentrations of
ketone bodies (D-(
3)-hydroxybutyrate +
acetoacetate) in rats bearing the Walker 256
carcinosarcoma were reduced by 45% (P less than 0.001) whereas the concentrations of
triglyceride and
free fatty acids were elevated by 223% (P less than 0.001) and 335% (P less than 0.001), respectively. Parallel with the changes in plasma, the livers of
tumor-bearing animals showed decreased concentrations of KB by 35% (P less than 0.05) and increased concentrations of TG and FFA by 49% (NS) and 15% (NS), respectively. In comparison with values for the control liver (fed ad libitum), the perfused liver of animals bearing the Walker 256
tumor formed 42% (P less than 0.05) and 75% (P less than 0.05) less
ketone bodies and CO2, respectively, from
oleate, while TG formation was enhanced by 33% (P less than 0.001). There was two- to threefold (P less than 0.001) enhancement of [1-14C]
leucine oxidation in vivo by the
tumor-bearing animals. The activities of
branched-chain amino acid aminotransferase and
branched-chain keto acid dehydrogenase were elevated by 70% (P less than 0.001) and 560% (P less than 0.001) respectively in the gastrocnemius muscle of the
tumor-bearing animals. The results of the investigation supported a second proposal of the hypothesis, namely, that
cancer-induced
cachexia resulted in the notable elevation in the concentration of
arginine vasopressin that was accompanied by parallel increases in the plasma, urine, and muscle concentrations of
prostaglandin E2. The proposals of the original hypothesis have been augmented to include roles for
PGE2 and the
cytokine cachectin/tumor necrosis factor which may engineer all of the events depicted in the original hypothesis.