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


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.

Publication DOI:
Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences
College of Health & Life Sciences > Chronic and Communicable Conditions
Additional Information: © 2002 Cancer Research UK Creative Commons Attribution-NonCommercial-Share-Alike 3.0 licence, subject to the conditions listed at
Uncontrolled Keywords: lipid-mobilizing factor,uncoupling proteins,cancer cachexia
Publication ISSN: 1532-1827
Last Modified: 17 Jun 2024 07:08
Date Deposited: 19 Aug 2019 08:49
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Related URLs: http://www.natu ... s/6600101a.html (Publisher URL)
PURE Output Type: Article
Published Date: 2002-02
Authors: Bing, C.
Russell, S.T. (ORCID Profile 0000-0002-5491-900X)
Beckett, E.E.
Collins, P.
Taylor, S.
Barraclough, R.
Tisdale, M.J.
Williams, G.

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