Expression of uncoupling proteins-1,-2 and-3 mRNA is induced by an adenocarcinoma-derived lipid-mobilizing factor

C. Bing, S.T. Russell, E.E. Beckett, P. Collins, S. Taylor, R. Barraclough, M.J. Tisdale, G. Williams

Research output: Contribution to journalArticle

Abstract

The abnormalities of lipid metabolism observed in cancer cachexia may be induced by a lipid-mobilizing factor produced by adenocarcinomas. The specific molecules and metabolic pathways that mediate the actions of lipid-mobilizing factor are not known. The mitochondrial uncoupling proteins-1, -2 and -3 are suggested to play essential roles in energy dissipation and disposal of excess lipid. Here, we studied the effects of lipid-mobilizing factor on the expression of uncoupling proteins-1, -2 and -3 in normal mice. Lipid-mobilizing factor isolated from the urine of cancer patients was injected intravenously into mice over a 52-h period, while vehicle was similarly given to controls. Lipid-mobilizing factor caused significant reductions in body weight (-10%, P=0.03) and fat mass (-20%, P<0.01) accompanied by a marked decrease in plasma leptin (-59%, P<0.01) and heavy lipid deposition in the liver. In brown adipose tissue, uncoupling protein-1 mRNA levels were elevated in lipid-mobilizing factor-treated mice (+96%, P<0.01), as were uncoupling proteins-2 and -3 (+57% and +37%, both P<0.05). Lipid-mobilizing factor increased uncoupling protein-2 mRNA in both skeletal muscle (+146%, P<0.05) and liver (+142%, P=0.03). The protein levels of uncoupling protein-1 in brown adipose tissue and uncoupling protein-2 in liver were also increased with lipid-mobilizing factor administration (+49% and +67%, both P=0.02). Upregulation by lipid-mobilizing factor of uncoupling proteins-1, -2 and -3 in brown adipose tissue, and of uncoupling protein-2 in skeletal muscle and liver, suggests that these uncoupling proteins may serve to utilize excess lipid mobilized during fat catabolism in cancer cachexia.
Original languageEnglish
Pages (from-to)612-618
Number of pages7
JournalBritish Journal of Cancer
Volume86
Issue number4
DOIs
Publication statusPublished - Feb 2002

Bibliographical note

© 2002 Cancer Research UK Creative Commons Attribution-NonCommercial-Share-Alike 3.0 licence, subject to the conditions listed at http://creativecommons.org/licences/by-nc-sa/3.0/

Keywords

  • lipid-mobilizing factor
  • uncoupling proteins
  • cancer cachexia

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  • Student Theses

    The mode of action of a lipid mobilising factor in cancer cachexia

    Author: Russell, S. T., Apr 2002

    Supervisor: Tisdale, M. J. (Supervisor)

    Student thesis: Doctoral ThesisDoctor of Philosophy

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