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

Bing C, Russell ST, Beckett EE, Collins P, Taylor S, Barraclough R, Tisdale MJ, Williams G - Br. J. Cancer (2002)

Bottom Line: 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.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).

View Article: PubMed Central - PubMed

Affiliation: Diabetes and Endocrinology Research Group, Department of Medicine, University of Liverpool, Liverpool L69 3G, UK. bing@iv.ac.uk

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.

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Histology of mouse liver. Fresh frozen tissue from five mice per group was sectioned on a cryostat and stained with Oil Red O. There was marked intracytoplasmic lipid accumulation in the liver from LMF-treated mice (B) but little in the vehicle-treated mice (A). Hepatocytes from all zones of the hepatic lobule were affected equally.
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fig7: Histology of mouse liver. Fresh frozen tissue from five mice per group was sectioned on a cryostat and stained with Oil Red O. There was marked intracytoplasmic lipid accumulation in the liver from LMF-treated mice (B) but little in the vehicle-treated mice (A). Hepatocytes from all zones of the hepatic lobule were affected equally.

Mentions: Haematoxylin and eosin staining of liver sections from LMF-treated mice showed no obvious signs of inflammation or other abnormality. However, Oil Red O staining showed abundant introcytoplasmic microdroplets of lipid deposited in hepatocytes in all zones of the hepatic lobule ( Figure 7AFigure 7


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

Bing C, Russell ST, Beckett EE, Collins P, Taylor S, Barraclough R, Tisdale MJ, Williams G - Br. J. Cancer (2002)

Histology of mouse liver. Fresh frozen tissue from five mice per group was sectioned on a cryostat and stained with Oil Red O. There was marked intracytoplasmic lipid accumulation in the liver from LMF-treated mice (B) but little in the vehicle-treated mice (A). Hepatocytes from all zones of the hepatic lobule were affected equally.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2375279&req=5

fig7: Histology of mouse liver. Fresh frozen tissue from five mice per group was sectioned on a cryostat and stained with Oil Red O. There was marked intracytoplasmic lipid accumulation in the liver from LMF-treated mice (B) but little in the vehicle-treated mice (A). Hepatocytes from all zones of the hepatic lobule were affected equally.
Mentions: Haematoxylin and eosin staining of liver sections from LMF-treated mice showed no obvious signs of inflammation or other abnormality. However, Oil Red O staining showed abundant introcytoplasmic microdroplets of lipid deposited in hepatocytes in all zones of the hepatic lobule ( Figure 7AFigure 7

Bottom Line: 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.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).

View Article: PubMed Central - PubMed

Affiliation: Diabetes and Endocrinology Research Group, Department of Medicine, University of Liverpool, Liverpool L69 3G, UK. bing@iv.ac.uk

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.

Show MeSH
Related in: MedlinePlus