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

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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 www.bjcancer.com

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  • 16 November 2011

    This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication

References

  1. Beck, SA & Tisdale, MJ (1987). Production of lipolytic and proteolytic factors by a murine tumor-producing cachexia in the host. Cancer Res, 47, 5919–5923.

    CAS  PubMed  Google Scholar 

  2. Beck, SA, Smith, KL & Tisdale, MJ (1991). Anticachectic and antitumor effect of eicosapentaenoic acid and its effect on protein turnover. Cancer Res, 51, 6089–6093.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Belsham, GJ, Denton, RM & Tanner, MJA (1980). 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, 192, 457–467.

    CAS  Article  Google Scholar 

  4. Carel, JC, Stunff, CL & Condamine, L (1999). Resistance to the lipolytic action of epinephrine: A new feature of protein Gs deficiency. J Clin Endocrinol Metab, 84, 4127–4131.

    CAS  Article  Google Scholar 

  5. Costa, G (1963). Cachexia, the metabolic component of neoplastic disease. Progr Exp Tumour Res, 3, 321–369.

    Article  Google Scholar 

  6. Dieudonne, M-N, Pecquery, R, Dausse, J-P & Giudicelli, Y (1993). Regulation of white adipocyte guanine nucleotide binding proteins Gsα and Giα1–2by testosterone in vivo: influence of regional fat distribution. Biochim Biophys Acta, 1176, 123–127.

    CAS  Article  Google Scholar 

  7. Gasic, S, Tian, B & Green, A (1999). Tumor necrosis factor α stimulates lipolysis in adipocytes by decreasing Gi protein concentrations. J Biol Chem, 274, 6770–6775.

    CAS  Article  Google Scholar 

  8. Green, A, Milligan, G & Dobias, SB (1992). Gi Down-regulation as a mechanism for heterologous desensitization in adipocytes. J Biol Chem, 267, 3223–3229.

    CAS  PubMed  Google Scholar 

  9. Groundwater, P, Beck, SA, Barton, C, Adamson, C, Ferrier, IN & Tisdale, MJ (1990). Alteration of serum and urinary lipolytic activity with weight loss in cachectic cancer patients. Br J Cancer, 62, 816–821.

    CAS  Article  Google Scholar 

  10. Hinsch, KD, Rosenthal, W, Spicher, K, Binder, T, Gauespohl, H, Frank, R, Scultz, G & Joost, HG (1988). Adipose plasma membranes contain two Gi subtypes but are devoid of Go. FEBS Lett, 238, 191–196.

    CAS  Article  Google Scholar 

  11. Hirai, K, Hussey, HJ, Barber, MD, Price, SA & Tisdale, MJ (1998). Biological evaluation of a lipid mobilizing factor (LMF) isolated from the urine of cancer patients. Cancer Res, 58, 2359–2365.

    CAS  PubMed  Google Scholar 

  12. Klein, S & Wolfe, RR (1990). Whole body lipolysis and triglyceride-fatty acid cycling in cachectic patients with oesophageal cancer. J Clin Invest, 86, 1403–1408.

    CAS  Article  Google Scholar 

  13. Levitzki, A (1987). Regulation of adenylate cyclase by hormones and G-proteins. Fed Eur Biochem Soc Lett, 211, 113–118.

    CAS  Article  Google Scholar 

  14. Milligan, G & Saggerson, ED (1990). Concurrent up-regulation of guanine-nucleotide-binding proteins Gi1α, Gi2α and Gi3α in adipocytes of hypothyroid rats. Biochem J, 270, 765–769.

    CAS  Article  Google Scholar 

  15. Price, SA & Tisdale, MJ (1998). Mechanism of inhibition of a tumor lipid-mobilizing factor by eicosapentaenoic acid. Cancer Res, 58, 4827–4831.

    CAS  PubMed  Google Scholar 

  16. Salomon, Y, Londos, C & Rodbell, M (1974). A highly sensitive adenylate cyclase assay. Anal Biochem, 58, 541–548.

    CAS  Article  Google Scholar 

  17. Thompson, MP, Koons, JE, Tan, ETH & Grigor, MR (1981). 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, 41, 3228–3232.

    CAS  PubMed  Google Scholar 

  18. Thompson, MP, Cooper, ST, Parry, BR & Tuckey, JA (1993). Increased expression of the mRNA for the hormone-sensitive lipase in adipose tissue of cancer patients. Biochim Biophys Acta, 1180, 236–241.

    CAS  Article  Google Scholar 

  19. Todorov, PT, McDevitt, TM, Meyer, DJ, Ueyama, H, Ohkubo, I & Tisdale, MJ (1998). Purification and characterization of a tumor lipid mobilizing factor (LMF). Cancer Res, 58, 2353–2358.

    CAS  PubMed  Google Scholar 

  20. Wieland, O (1974). Glycerol UV method. Methods of Enzymatic Analysis, Bergmeyer HU (ed) 1404–1409, Academic Press: London

    Google Scholar 

  21. Wigmore, SJ, Ross, JA, Falconer, JS, Plester, CE, Tisdale, MJ, Carter, DC & Fearon, KCH (1996). The effect of polyunsaturated fatty acids on the progress of cachexia in patients with pancreatic cancer. Nutrition, 12, S27–S30.

    CAS  Article  Google Scholar 

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From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

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Islam-Ali, B., Khan, S., Price, S. et al. Modulation of adipocyte G-protein expression in cancer cachexia by a lipid-mobilizing factor (LMF). Br J Cancer 85, 758–763 (2001). https://doi.org/10.1054/bjoc.2001.1992

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Keywords

  • lipid-mobilizing factor
  • G-protein expression
  • lipolysis

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