Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1991 Jul 15;277(Pt 2):321–326. doi: 10.1042/bj2770321

Metabolic substrate utilization by tumour and host tissues in cancer cachexia.

H D Mulligan 1, M J Tisdale 1
PMCID: PMC1151235  PMID: 1859359

Abstract

Utilization of metabolic substrates in tumour and host tissues was determined in the presence or absence of two colonic tumours, the MAC16, which is capable of inducing cachexia in recipient animals, and the MAC13, which is of the same histological type, but without the effect on host body composition. Glucose utilization by different tissues was determined in vivo by the 2-deoxyglucose tracer technique. Glucose utilization by the MAC13 tumour was significantly higher than by the MAC16 tumour, and in animals bearing tumours of either type the tumour was the second major consumer of glucose after the brain. This extra demand for glucose was accompanied by a marked decrease in glucose utilization by the epididymal fat-pads, testes, colon, spleen, kidney and, in particular, the brain, in tumour-bearing animals irrespective of cachexia. The decrease in glucose consumption by the brain was at least as high as the metabolic demand by the tumour. This suggests that the tissues of tumour-bearing animals adapt to use substrates other than glucose and that alterations in glucose utilization are not responsible for the cachexia. Studies in vitro showed that brain metabolism in the tumour-bearing state was maintained by an increased use of lactate and 3-hydroxybutyrate, accompanied by a 50% increase in 3-oxoacid CoA-transferase. This was supported by studies in vivo which showed an increased metabolism of 3-hydroxybutyrate in tumour-bearing animals. Thus ketone bodies may be utilized as a metabolic fuel during the cancer-bearing state, even though the nutritional conditions mimic the fed state.

Full text

PDF
321

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beck S. A., Tisdale M. J. Production of lipolytic and proteolytic factors by a murine tumor-producing cachexia in the host. Cancer Res. 1987 Nov 15;47(22):5919–5923. [PubMed] [Google Scholar]
  2. Bernstein I. L. Etiology of anorexia in cancer. Cancer. 1986 Oct 15;58(8 Suppl):1881–1886. doi: 10.1002/1097-0142(19861015)58:8+<1881::aid-cncr2820581415>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
  3. Bibby M. C., Double J. A., Ali S. A., Fearon K. C., Brennan R. A., Tisdale M. J. Characterization of a transplantable adenocarcinoma of the mouse colon producing cachexia in recipient animals. J Natl Cancer Inst. 1987 Mar;78(3):539–546. [PubMed] [Google Scholar]
  4. Brennan M. F. Uncomplicated starvation versus cancer cachexia. Cancer Res. 1977 Jul;37(7 Pt 2):2359–2364. [PubMed] [Google Scholar]
  5. Ferré P., Leturque A., Burnol A. F., Penicaud L., Girard J. A method to quantify glucose utilization in vivo in skeletal muscle and white adipose tissue of the anaesthetized rat. Biochem J. 1985 May 15;228(1):103–110. doi: 10.1042/bj2280103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Groundwater P., Beck S. A., Barton C., Adamson C., Ferrier I. N., Tisdale M. J. Alteration of serum and urinary lipolytic activity with weight loss in cachectic cancer patients. Br J Cancer. 1990 Nov;62(5):816–821. doi: 10.1038/bjc.1990.384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Holroyde C. P., Gabuzda T. G., Putnam R. C., Paul P., Reichard G. A. Altered glucose metabolism in metastatic carcinoma. Cancer Res. 1975 Dec;35(12):3710–3714. [PubMed] [Google Scholar]
  8. Hume D. A., Weidemann M. J. Role and regulation of glucose metabolism in proliferating cells. J Natl Cancer Inst. 1979 Jan;62(1):3–8. [PubMed] [Google Scholar]
  9. Lundholm K., Holm G., Scherstén T. Insulin resistance in patients with cancer. Cancer Res. 1978 Dec;38(12):4665–4670. [PubMed] [Google Scholar]
  10. Mészáros K., Lang C. H., Bagby G. J., Spitzer J. J. Tumor necrosis factor increases in vivo glucose utilization of macrophage-rich tissues. Biochem Biophys Res Commun. 1987 Nov 30;149(1):1–6. doi: 10.1016/0006-291x(87)91596-8. [DOI] [PubMed] [Google Scholar]
  11. Nakamura K., Nakajima Y., Nakamura Y. Suppression of glucose utilization of murine peritoneal exudate macrophages by body fluids from cancer patients and identification of the susceptible enzyme. J Natl Cancer Inst. 1986 Nov;77(5):1035–1038. [PubMed] [Google Scholar]
  12. Nakashima R. A., Paggi M. G., Pedersen P. L. Contributions of glycolysis and oxidative phosphorylation to adenosine 5'-triphosphate production in AS-30D hepatoma cells. Cancer Res. 1984 Dec;44(12 Pt 1):5702–5706. [PubMed] [Google Scholar]
  13. Nolop K. B., Rhodes C. G., Brudin L. H., Beaney R. P., Krausz T., Jones T., Hughes J. M. Glucose utilization in vivo by human pulmonary neoplasms. Cancer. 1987 Dec 1;60(11):2682–2689. doi: 10.1002/1097-0142(19871201)60:11<2682::aid-cncr2820601118>3.0.co;2-h. [DOI] [PubMed] [Google Scholar]
  14. Owen O. E., Morgan A. P., Kemp H. G., Sullivan J. M., Herrera M. G., Cahill G. F., Jr Brain metabolism during fasting. J Clin Invest. 1967 Oct;46(10):1589–1595. doi: 10.1172/JCI105650. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Sauer L. A., Dauchy R. T. In vivo lactate production and utilization by Jensen sarcoma and Morris hepatoma 7288CTC. Cancer Res. 1986 Feb;46(2):689–693. [PubMed] [Google Scholar]
  16. Sauer L. A., Stayman J. W., 3rd, Dauchy R. T. Amino acid, glucose, and lactic acid utilization in vivo by rat tumors. Cancer Res. 1982 Oct;42(10):4090–4097. [PubMed] [Google Scholar]
  17. Shambaugh G. E., 3rd Ketone body metabolism in the mother and fetus. Fed Proc. 1985 Apr;44(7):2347–2351. [PubMed] [Google Scholar]
  18. Shapot V. S. Some biochemical aspects of the relationship between the tumor and the host. Adv Cancer Res. 1972;15:253–286. doi: 10.1016/s0065-230x(08)60377-2. [DOI] [PubMed] [Google Scholar]
  19. Tisdale M. J., Brennan R. A. Metabolic substrate utilization by a tumour cell line which induces cachexia in vivo. Br J Cancer. 1986 Oct;54(4):601–606. doi: 10.1038/bjc.1986.215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Warnold I., Lundholm K., Scherstén T. Energy balance and body composition in cancer patients. Cancer Res. 1978 Jun;38(6):1801–1807. [PubMed] [Google Scholar]
  21. Waterhouse C., Jeanpretre N., Keilson J. Gluconeogenesis from alanine in patients with progressive malignant disease. Cancer Res. 1979 Jun;39(6 Pt 1):1968–1972. [PubMed] [Google Scholar]
  22. Waterhouse C., Kemperman J. H. Carbohydrate metabolism in subjects with cancer. Cancer Res. 1971 Sep;31(9):1273–1278. [PubMed] [Google Scholar]
  23. Williamson D. H., Bates M. W., Page M. A., Krebs H. A. Activities of enzymes involved in acetoacetate utilization in adult mammalian tissues. Biochem J. 1971 Jan;121(1):41–47. doi: 10.1042/bj1210041. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES