Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Advertisement

British Journal of Cancer
  • View all journals
  • Search
  • My Account Login
  • Content Explore content
  • About the journal
  • Publish with us
  • Sign up for alerts
  • RSS feed
  1. nature
  2. british journal of cancer
  3. regular article
  4. article
Modulation of adipocyte G-protein expression in cancer cachexia by a lipid-mobilizing factor (LMF)
Download PDF
Download PDF
  • Regular Article
  • Open access
  • Published: 28 August 2001

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

  • B Islam-Ali1,
  • S Khan1,
  • S A Price1 &
  • …
  • M J Tisdale1 

British Journal of Cancer volume 85, pages 758–763 (2001)Cite this article

  • 1184 Accesses

  • 51 Citations

  • 3 Altmetric

  • Metrics details

This article has been updated

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

Similar content being viewed by others

Adipocytes reprogram cancer cell metabolism by diverting glucose towards glycerol-3-phosphate thereby promoting metastasis

Article 31 August 2023

Single-cell sequencing unveils key contributions of immune cell populations in cancer-associated adipose wasting

Article Open access 15 November 2022

GPSM1 impairs metabolic homeostasis by controlling a pro-inflammatory pathway in macrophages

Article Open access 25 November 2022

Article PDF

Change history

  • 16 November 2011

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

References

  • 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 

  • 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  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

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

    Article  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 

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

    Article  CAS  PubMed  Google Scholar 

  • 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 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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 

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

    Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pharmaceutical Sciences Research Institute, Aston University, Birmingham, B4 7ET, UK

    B Islam-Ali, S Khan, S A Price & M J Tisdale

Authors
  1. B Islam-Ali
    View author publications

    Search author on:PubMed Google Scholar

  2. S Khan
    View author publications

    Search author on:PubMed Google Scholar

  3. S A Price
    View author publications

    Search author on:PubMed Google Scholar

  4. M J Tisdale
    View author publications

    Search author on:PubMed Google Scholar

Rights and permissions

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/

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received: 07 March 2001

  • Revised: 11 June 2001

  • Accepted: 12 June 2001

  • Published: 28 August 2001

  • Issue date: 31 August 2001

  • DOI: https://doi.org/10.1054/bjoc.2001.1992

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Keywords

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

This article is cited by

  • Significance of preoperative evaluation of modified advanced lung cancer inflammation index for patients with resectable non-small cell lung cancer

    • Seijiro Sato
    • Ryo Sezaki
    • Hirohiko Shinohara

    General Thoracic and Cardiovascular Surgery (2024)

  • The burning furnace: Alteration in lipid metabolism in cancer-associated cachexia

    • Mit Joshi
    • Bhoomika M. Patel

    Molecular and Cellular Biochemistry (2022)

  • Preclinical and clinical studies on cancer-associated cachexia

    • D. Brooke Widner
    • D. Clark Files
    • Yusuke Shiozawa

    Frontiers in Biology (2018)

  • Cachexia in patients with oesophageal cancer

    • Poorna Anandavadivelan
    • Pernilla Lagergren

    Nature Reviews Clinical Oncology (2016)

  • Proteomic profiling of the hypothalamus in a mouse model of cancer-induced anorexia-cachexia

    • R Ihnatko
    • C Post
    • A Blomqvist

    British Journal of Cancer (2013)

Download PDF

Advertisement

Explore content

  • Research articles
  • Reviews & Analysis
  • News & Comment
  • Current issue
  • Collections
  • Follow us on Twitter
  • Sign up for alerts
  • RSS feed

About the journal

  • Journal Information
  • Open access publishing
  • About the Editors
  • Contact
  • Special Issues
  • For Advertisers
  • Subscribe

Publish with us

  • For Authors & Referees
  • Language editing services
  • Submit manuscript

Search

Advanced search

Quick links

  • Explore articles by subject
  • Find a job
  • Guide to authors
  • Editorial policies

British Journal of Cancer (Br J Cancer)

ISSN 1532-1827 (online)

ISSN 0007-0920 (print)

nature.com sitemap

About Nature Portfolio

  • About us
  • Press releases
  • Press office
  • Contact us

Discover content

  • Journals A-Z
  • Articles by subject
  • protocols.io
  • Nature Index

Publishing policies

  • Nature portfolio policies
  • Open access

Author & Researcher services

  • Reprints & permissions
  • Research data
  • Language editing
  • Scientific editing
  • Nature Masterclasses
  • Research Solutions

Libraries & institutions

  • Librarian service & tools
  • Librarian portal
  • Open research
  • Recommend to library

Advertising & partnerships

  • Advertising
  • Partnerships & Services
  • Media kits
  • Branded content

Professional development

  • Nature Awards
  • Nature Careers
  • Nature Conferences

Regional websites

  • Nature Africa
  • Nature China
  • Nature India
  • Nature Japan
  • Nature Middle East
  • Privacy Policy
  • Use of cookies
  • Legal notice
  • Accessibility statement
  • Terms & Conditions
  • Your US state privacy rights
Springer Nature

© 2025 Springer Nature Limited