Effect of a cachectic factor on carbohydrate metabolism and attenuation byeicosapentaenoic acid

The effect of a proteolysis-inducing factor (PIF), produced by cachexia-ind ucing tumours on glucose utilization by different tissues and the effect of pretreatment with the polyunsaturated fatty acid eicosapentaenoic acid (EP A), has been determined using the 2-deoxyglucose tracer technique. Mice rec eiving PIF showed a profound depression of body weight (2.3 g) over a 24-h period, which was completely abolished by pretreatment with a monoclonal an tibody to PIF or by 3 days pretreatment with EPA at 500 mg kg(-1). Animals receiving PIF exhibited a marked hypoglycaemia, which was effectively rever sed by both antibody and EPA pretreatment. There was an increase in glucose utilization by brain, heart and brown fat, but a decrease by kidney, white fat, diaphragm and gastrocnemius muscle after administration of PIF. Chang es in organ glucose consumption were attenuated by either monoclonal antibo dy, EPA, or both. There was a decrease in 2-deoxyglucose uptake by C2C12 my oblasts in vitro, which was attenuated by EPA. This suggests a direct effec t of PIF on glucose uptake by skeletal muscle. These results suggest that i n addition to a direct catabolic effect on skeletal muscle PIF has a profou nd effect on glucose utilization during cachexia.