Hj. Hussey et Mj. Tisdale, Effect of a cachectic factor on carbohydrate metabolism and attenuation byeicosapentaenoic acid, BR J CANC, 80(8), 1999, pp. 1231-1235
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.