Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 2001 Sep;85(5):758–763. doi: 10.1054/bjoc.2001.1992

Modulation of adipocyte G-protein expression in cancer cachexia by a lipid-mobilizing factor (LMF)

B Islam-Ali 1, S Khan 1, S A Price 1, M J Tisdale 1
PMCID: PMC2364135  PMID: 11531264

Abstract

Adipocytes isolated from cachectic mice bearing the MAC 16 tumour showed over a 3-fold increase in lipolytic response to both low concentrations of isoprenaline and a tumour-derived lipid mobilizing factor (LMF). This was reflected by an enhanced stimulation of adenylate cyclase in plasma membrane fractions of adipocytes in the presence of both factors. There was no up-regulation of adenylate cyclase in response to forskolin, suggesting that the effect arose from a change in receptor number or G-protein expression. Immunoblotting of adipocyte membranes from mice bearing the MAC16 tumour showed an increased expression of Gαs up to 10% weight loss and a reciprocal decrease in Gα. There was also an increased expression of Gαs and a decrease in Gα in adipose tissue from a patient with cancer-associated weight loss compared with a non-cachectic cancer patient. The changes in G-protein expression were also seen in adipose tissue of normal mice administered pure LMF as well as in 3T3L1 adipocytes in vitro. The changes in G-protein expression induced by LMF were attenuated by the polyunsaturated fatty acid, eicosapentaenoic acid (EPA). This suggests that this tumour-derived lipolytic factor acts to sensitize adipose tissue to lipolytic stimuli, and that this effect is attenuated by EPA, which is known to preserve adipose tissue in cancer cachexia. © 2001 Cancer Research Campaign

Keywords: lipid-mobilizing factor, G-protein expression, lipolysis

Full Text

The Full Text of this article is available as a PDF (99.6 KB).

Selected References

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

  1. Beck S. A., Smith K. L., Tisdale M. J. Anticachectic and antitumor effect of eicosapentaenoic acid and its effect on protein turnover. Cancer Res. 1991 Nov 15;51(22):6089–6093. [PubMed] [Google Scholar]
  2. 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]
  3. Belsham G. J., Denton R. M., Tanner M. J. Use of a novel rapid preparation of fat-cell plasma membranes employing Percoll to investigate the effects of insulin and adrenaline on membrane protein phosphorylation within intact fat-cells. Biochem J. 1980 Nov 15;192(2):457–467. doi: 10.1042/bj1920457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Carel J. C., Le Stunff C., Condamine L., Mallet E., Chaussain J. L., Adnot P., Garabédian M., Bougnères P. Resistance to the lipolytic action of epinephrine: a new feature of protein Gs deficiency. J Clin Endocrinol Metab. 1999 Nov;84(11):4127–4131. doi: 10.1210/jcem.84.11.6145. [DOI] [PubMed] [Google Scholar]
  5. Dieudonne M. N., Pecquery R., Dausse J. P., Giudicelli Y. Regulation of white adipocyte guanine nucleotide binding proteins Gs alpha and Gi alpha 1-2 by testosterone in vivo: influence of regional fat distribution. Biochim Biophys Acta. 1993 Mar 10;1176(1-2):123–127. doi: 10.1016/0167-4889(93)90186-s. [DOI] [PubMed] [Google Scholar]
  6. Gasic S., Tian B., Green A. Tumor necrosis factor alpha stimulates lipolysis in adipocytes by decreasing Gi protein concentrations. J Biol Chem. 1999 Mar 5;274(10):6770–6775. doi: 10.1074/jbc.274.10.6770. [DOI] [PubMed] [Google Scholar]
  7. Green A., Milligan G., Dobias S. B. Gi down-regulation as a mechanism for heterologous desensitization in adipocytes. J Biol Chem. 1992 Feb 15;267(5):3223–3229. [PubMed] [Google Scholar]
  8. 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]
  9. Hinsch K. D., Rosenthal W., Spicher K., Binder T., Gausepohl H., Frank R., Schultz G., Joost H. G. Adipocyte plasma membranes contain two Gi subtypes but are devoid of Go. FEBS Lett. 1988 Sep 26;238(1):191–196. doi: 10.1016/0014-5793(88)80254-0. [DOI] [PubMed] [Google Scholar]
  10. Hirai K., Hussey H. J., Barber M. D., Price S. A., Tisdale M. J. Biological evaluation of a lipid-mobilizing factor isolated from the urine of cancer patients. Cancer Res. 1998 Jun 1;58(11):2359–2365. [PubMed] [Google Scholar]
  11. Klein S., Wolfe R. R. Whole-body lipolysis and triglyceride-fatty acid cycling in cachectic patients with esophageal cancer. J Clin Invest. 1990 Nov;86(5):1403–1408. doi: 10.1172/JCI114854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Levitzki A. Regulation of adenylate cyclase by hormones and G-proteins. FEBS Lett. 1987 Jan 26;211(2):113–118. doi: 10.1016/0014-5793(87)81419-9. [DOI] [PubMed] [Google Scholar]
  13. Milligan G., Saggerson E. D. Concurrent up-regulation of guanine-nucleotide-binding proteins Gi1 alpha, Gi2 alpha and Gi3 alpha in adipocytes of hypothyroid rats. Biochem J. 1990 Sep 15;270(3):765–769. doi: 10.1042/bj2700765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Price S. A., Tisdale M. J. Mechanism of inhibition of a tumor lipid-mobilizing factor by eicosapentaenoic acid. Cancer Res. 1998 Nov 1;58(21):4827–4831. [PubMed] [Google Scholar]
  15. Salomon Y., Londos C., Rodbell M. A highly sensitive adenylate cyclase assay. Anal Biochem. 1974 Apr;58(2):541–548. doi: 10.1016/0003-2697(74)90222-x. [DOI] [PubMed] [Google Scholar]
  16. Thompson M. P., Cooper S. T., Parry B. R., Tuckey J. A. Increased expression of the mRNA for hormone-sensitive lipase in adipose tissue of cancer patients. Biochim Biophys Acta. 1993 Jan 22;1180(3):236–242. doi: 10.1016/0925-4439(93)90044-2. [DOI] [PubMed] [Google Scholar]
  17. Thompson M. P., Koons J. E., Tan E. T., Grigor M. R. Modified lipoprotein lipase activities, rates of lipogenesis, and lipolysis as factors leading to lipid depletion in C57BL mice bearing the preputial gland tumor, ESR-586. Cancer Res. 1981 Aug;41(8):3228–3232. [PubMed] [Google Scholar]
  18. Todorov P. T., McDevitt T. M., Meyer D. J., Ueyama H., Ohkubo I., Tisdale M. J. Purification and characterization of a tumor lipid-mobilizing factor. Cancer Res. 1998 Jun 1;58(11):2353–2358. [PubMed] [Google Scholar]
  19. Wigmore S. J., Ross J. A., Falconer J. S., Plester C. E., Tisdale M. J., Carter D. C., Fearon K. C. The effect of polyunsaturated fatty acids on the progress of cachexia in patients with pancreatic cancer. Nutrition. 1996 Jan;12(1 Suppl):S27–S30. doi: 10.1016/0899-9007(96)90014-3. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES