Effect of a tumour-derived lipid-mobilising factor on glucose and lipid metabolism in vivo.
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.
Pharmaceutical Sciences Research Institute, Aston University, Birmingham B4 7ET, UK.
S T
ST
Russell
M J
MJ
Tisdale
D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D002100:Cachexia / Q000209:etiology / Q000652:urine*; D050260:Carbohydrate Metabolism; D003847:Deoxyglucose / Q000493:pharmacokinetics; D004734:Energy Metabolism / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D050356:Lipid Metabolism; D008053:Lipid Mobilization / Q000187:drug effects* / Q000502:physiology; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018482:Muscle, Skeletal / Q000378:metabolism; D009928:Organ Specificity; D010190:Pancreatic Neoplasms / Q000150:complications / Q000652:urine; D010455:Peptides / Q000494:pharmacology* / Q000652:urine; D015431:Weight Loss / Q000187:drug effects
D005230:Fatty Acids, Nonesterified; D010455:Peptides; C008287:lipid mobilizing substance; D003847:Deoxyglucose; D005947:Glucose