The regulation of fatty acid and branched-chain amino acid oxidation in cancer cachectic rats: a proposed role for a cytokine, eicosanoid, and hormone trilogy.
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.
Department of Biochemistry, Faculty of Science, Australian National University, Canberra.
R A
RA
Siddiqui
J F
JF
Williams
D000597:Amino Acids, Branched-Chain / Q000378:metabolism*; D000818:Animals; D001127:Arginine Vasopressin / Q000502:physiology*; D002279:Carcinoma 256, Walker / Q000378:metabolism*; D015232:Dinoprostone / Q000502:physiology*; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D000597:Amino Acids, Branched-Chain; D005227:Fatty Acids; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D001127:Arginine Vasopressin; D015232:Dinoprostone