Utilization of metabolic substrates in tumour and host tissues was determined in the presence or absence of two colonic tumours, the MAC16, which is capable of inducing cachexia in recipient animals, and the MAC13, which is of the same histological type, but without the effect on host body composition. Glucose utilization by different tissues was determined in vivo by the 2-deoxyglucose tracer technique. Glucose utilization by the MAC13 tumour was significantly higher than by the MAC16 tumour, and in animals bearing tumours of either type the tumour was the second major consumer of glucose after the brain. This extra demand for glucose was accompanied by a marked decrease in glucose utilization by the epididymal fat-pads, testes, colon, spleen, kidney and, in particular, the brain, in tumour-bearing animals irrespective of cachexia. The decrease in glucose consumption by the brain was at least as high as the metabolic demand by the tumour. This suggests that the tissues of tumour-bearing animals adapt to use substrates other than glucose and that alterations in glucose utilization are not responsible for the cachexia. Studies in vitro showed that brain metabolism in the tumour-bearing state was maintained by an increased use of lactate and 3-hydroxybutyrate, accompanied by a 50% increase in 3-oxoacid CoA-transferase. This was supported by studies in vivo which showed an increased metabolism of 3-hydroxybutyrate in tumour-bearing animals. Thus ketone bodies may be utilized as a metabolic fuel during the cancer-bearing state, even though the nutritional conditions mimic the fed state.

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Summary Although animals bearing the MAC16 colon adenocarcinoma showed progressive weight loss, the average food consumption (15.1 ± 0.6 Kcal day-') did not differ from non tumour-bearing controls (15.3 ± 0.3 Kcal day-'), while animals bearing a related colon adenocarcinoma, MAC13, which had no effect on body weight had a significantly (P< 0.01) elevated food intake (16.4 ± 0.3 Kcal day-') above controls. Weight loss in animals bearing the MAC1 6 tumour was associated with a significant reduction in the percentage contribution of the kidneys, colon and epididymal fat pads to the total body weight. (Tisdale & Leung, 1988). This suggests that host lipogenesis may be increased in the tumour-bearing state irrespective of the effect of the tumour on host adipose tissue.Tumours require fatty acids for oxidative metabolism, for membrane lipids and as a source of metabolic regulators such as eicosanoids and diacylglycerol. Although some tumours have been reported to synthesise fatty acids de novo it is generally accepted that most of the host lipid requirements are met from the host (Spector, 1975). In this context, we have compared the synthetic ability of the two colon adenocarcinomas, MAC16 and MAC13 both in vitro and in vivo to ascertain whether differences in host lipid depletion arise from differences in the biosynthetic capacity of the two tumours. In addition the lipogenic response of host tissues to the presence of the two tumours has been evaluated. Material and methodsPure strain NMRI mice were bred in our own colony and were fed a rat and mouse breeding diet (Pilsbury, Birmingham, UK) and water ad libitum. Fragments of either the MAC 16 or MAC13 tumour were implanted into the flank of male NMRI mice by means of a trocar as described (Beck & Tisdale, 1987;Bibby et al., 1987). Animals bearing the MAC16 tumour developed weight loss 10 to 12 days following tumour transplantation (average tumour weight 200 mg) and when weight loss was prolonged the animals were regarded as cachectic (average weight loss 2 to 4 g). Animals bearing the MAC13 tumour were used 10 to 12 days following tumour transplantation, when the tumour became palpable (average weight 200 mg), and were matched in body weight to those bearing the MAC16 tumour.Both the MAC13 and MAC16 cell lines were derived from the solid tumours and were maintained in vitro in RPMI 1640 tissue culture medium containing 10% foetal calf serum under an atmosphere of 5% CO2 in air.Determination of lipogenesis from glucose D-[U-'4C] Glucose (sp.act. 270 m Cimmol') (Amersham International, Bucks, UK) was administered to male NMRI mice by i.p. injection (250 yCi Kg-') in 0.2 ml of normal saline. Three hours after injection, animals were anaesthetised and blood was removed by cardiac puncture. The following organs were dissected out and weighed; epididymal fat pads, spleen, liver, kidneys, colon, brain and tumour. Lipids were extracted from the blood and organs by the method of Stansbie et al. (1976). Organs were heated in 3 ml of 30% (w/v) KOH for 15 min at 70°C, follow...

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Summary The growth rate of the MAC16 tumour in cachectic animals was significantly enhanced by the hypolipidemic agent bezafibrate, while the growth rate of a histologically similar tumour, the MAC13, which grows without an effect on host body compartments was unaffected. Growth of the MAC16 in vitro was unaffected by bezafibrate, suggesting that it was an in vivo phenomenon only. The stimulatory effect of bezafibrate correlated with the maximum plasma levels of free fatty acids (FFA) arising from the catabolism of adipose tissue. Accumulation of '4C-lipid from 1-'4C-triolein administered by intragastric intubation was enhanced in heart, gastrocnemius muscle and tumour of bezafibrate treated animals, while the total lipid absorption did not differ from solvent treated controls. The increased lipid accumulation in the heart, but not the tumour correlated with an increased tissue lipoprotein lipase level. The increased tumour level may arise from an increased uptake of FFA arising from a weakening of the bonds between FFA and albumin. These results suggest that growth of certain tumours is dependent on maintaining sufficient lipid levels and that the lipid mobilising effect of the tumour may be necessary to sustain tumour growth.