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Effect of a tumour-derived lipid-mobilising factor on glucose and lipid metabolism in vivo.

Russell ST, Tisdale MJ - Br. J. Cancer (2002)

Bottom Line: The tissue glucose metabolic rate was increased almost three-fold in brain, accounting for the ability of lipid mobilising factor to decrease blood glucose levels.Lipid mobilising factor also increased overall lipid oxidation, as determined by the production of 14CO2 from [14C carboxy] triolein, being 67% greater than phosphate buffered saline controls over a 24 h period.There was a significant increase in [14C] lipid accumulation in plasma, liver and white and brown adipose tissue after administration of lipid mobilising factor.

View Article: PubMed Central - PubMed

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

ABSTRACT
Treatment of ex-breeder male NMRI mice with lipid mobilising factor isolated from the urine of cachectic cancer patients, caused a significant increase in glucose oxidation to CO2 compared with control mice receiving phosphate buffered saline. Glucose utilisation by various tissues was determined by the 2-deoxyglucose tracer technique and shown to be elevated in brain, heart, brown adipose tissue and gastrocnemius muscle. The tissue glucose metabolic rate was increased almost three-fold in brain, accounting for the ability of lipid mobilising factor to decrease blood glucose levels. Lipid mobilising factor also increased overall lipid oxidation, as determined by the production of 14CO2 from [14C carboxy] triolein, being 67% greater than phosphate buffered saline controls over a 24 h period. There was a significant increase in [14C] lipid accumulation in plasma, liver and white and brown adipose tissue after administration of lipid mobilising factor. These results suggest that changes in carbohydrate metabolism and loss of adipose tissue, together with an increased whole body fatty acid oxidation in cachectic cancer patients, may arise from tumour production of lipid mobilising factor.

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Electrophoretic separation of proteins on a 12% SDS polyacrylamide gel. Lane 1 molecular weight markers; Lane 2 LMF (5 μg protein) eluted from Resource-Iso column at 0.6 M (NH4)2SO4.
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fig1: Electrophoretic separation of proteins on a 12% SDS polyacrylamide gel. Lane 1 molecular weight markers; Lane 2 LMF (5 μg protein) eluted from Resource-Iso column at 0.6 M (NH4)2SO4.

Mentions: LMF was purified from the urine of weight losing patients with pancreatic cancer using a combination of batch extraction on DEAE cellulose and hydrophobic interaction chromatography as previously described (Todorov et al, 1998). Urine was centrifuged at 3000 g for 10 min to remove particulate material and diluted with 4 vol 10 mM Tris. HCl, pH 8.0. DEAE cellulose (10 g l−1 of original urine) was then added and the mixture was stirred for 2 h at 4°C. The LMF–DEAE cellulose complex was isolated by low speed centrifugation, and LMF eluted with 0.5 M NaCl in 10 mM Tris. HCl, pH 8.0. Bioactivity was monitored by the release of glycerol from freshly isolated epididymal adipocytes (Beck and Tisdale, 1987). The eluate was equilibrated against PBS and concentrated to 1 ml before further purification using a Resource-Iso HPLC column (Pharmacia Biotech, St Albans, Herts, UK) employing a decreasing (NH4)2SO4 concentration from 1.5 M. Active fractions containing LMF eluted at 0.6 M (NH4)2SO4 and were desalted before use by washing five times against PBS using an Amicon filtration cell. LMF eluted mainly as a single protein band of Mr 43 000, as determined by Coomassie blue staining of a 12% SDS polyacrylamide gel (Figure 1Figure 1


Effect of a tumour-derived lipid-mobilising factor on glucose and lipid metabolism in vivo.

Russell ST, Tisdale MJ - Br. J. Cancer (2002)

Electrophoretic separation of proteins on a 12% SDS polyacrylamide gel. Lane 1 molecular weight markers; Lane 2 LMF (5 μg protein) eluted from Resource-Iso column at 0.6 M (NH4)2SO4.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376149&req=5

fig1: Electrophoretic separation of proteins on a 12% SDS polyacrylamide gel. Lane 1 molecular weight markers; Lane 2 LMF (5 μg protein) eluted from Resource-Iso column at 0.6 M (NH4)2SO4.
Mentions: LMF was purified from the urine of weight losing patients with pancreatic cancer using a combination of batch extraction on DEAE cellulose and hydrophobic interaction chromatography as previously described (Todorov et al, 1998). Urine was centrifuged at 3000 g for 10 min to remove particulate material and diluted with 4 vol 10 mM Tris. HCl, pH 8.0. DEAE cellulose (10 g l−1 of original urine) was then added and the mixture was stirred for 2 h at 4°C. The LMF–DEAE cellulose complex was isolated by low speed centrifugation, and LMF eluted with 0.5 M NaCl in 10 mM Tris. HCl, pH 8.0. Bioactivity was monitored by the release of glycerol from freshly isolated epididymal adipocytes (Beck and Tisdale, 1987). The eluate was equilibrated against PBS and concentrated to 1 ml before further purification using a Resource-Iso HPLC column (Pharmacia Biotech, St Albans, Herts, UK) employing a decreasing (NH4)2SO4 concentration from 1.5 M. Active fractions containing LMF eluted at 0.6 M (NH4)2SO4 and were desalted before use by washing five times against PBS using an Amicon filtration cell. LMF eluted mainly as a single protein band of Mr 43 000, as determined by Coomassie blue staining of a 12% SDS polyacrylamide gel (Figure 1Figure 1

Bottom Line: The tissue glucose metabolic rate was increased almost three-fold in brain, accounting for the ability of lipid mobilising factor to decrease blood glucose levels.Lipid mobilising factor also increased overall lipid oxidation, as determined by the production of 14CO2 from [14C carboxy] triolein, being 67% greater than phosphate buffered saline controls over a 24 h period.There was a significant increase in [14C] lipid accumulation in plasma, liver and white and brown adipose tissue after administration of lipid mobilising factor.

View Article: PubMed Central - PubMed

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

ABSTRACT
Treatment of ex-breeder male NMRI mice with lipid mobilising factor isolated from the urine of cachectic cancer patients, caused a significant increase in glucose oxidation to CO2 compared with control mice receiving phosphate buffered saline. Glucose utilisation by various tissues was determined by the 2-deoxyglucose tracer technique and shown to be elevated in brain, heart, brown adipose tissue and gastrocnemius muscle. The tissue glucose metabolic rate was increased almost three-fold in brain, accounting for the ability of lipid mobilising factor to decrease blood glucose levels. Lipid mobilising factor also increased overall lipid oxidation, as determined by the production of 14CO2 from [14C carboxy] triolein, being 67% greater than phosphate buffered saline controls over a 24 h period. There was a significant increase in [14C] lipid accumulation in plasma, liver and white and brown adipose tissue after administration of lipid mobilising factor. These results suggest that changes in carbohydrate metabolism and loss of adipose tissue, together with an increased whole body fatty acid oxidation in cachectic cancer patients, may arise from tumour production of lipid mobilising factor.

Show MeSH
Related in: MedlinePlus