Lipogenesis in tumour and host tissues in mice bearing colonic adenocarcinomas

Abstract

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...

Humoral mediation for cachexia in tumour-bearing rats

“…Yet undernutrition undoubtedly occurs in these tumour hosts, thus adding a further component to the complexity of their metabolic perturbations. Studying a different model of cachexia, Mulligan & Tisdale (1991) have recently shown that only tumour-bearing animals that failed to adjust their food intake in the presence of metabolic disturbances underwent dramatic weight loss.…”

Mechanisms to explain wasting of muscle and fat in cancer cachexia

“…In tumour-bearing animals with a high degree of cachexia, there is also an important association between decreased LPL activity and hypertriglyceridaemia [70,71]. Another factor that could contribute to the elevation in circulating triacylglycerols is an increase in liver lipogenesis [72].…”

Lipid metabolism in cancer cachexia

“…Thus the tissues of cachectic animals have an increased utilisation of fat as an energy source, suggesting that the overall energy requirements are higher in the cachectic state. This increased requirement for lipid is shown not only by catabolism of adipose tissue, but also by an increased conversion of glucose to lipids (Mulligan & Tisdale, 1991b) and by an increased [14C]lipid accumulation by the MAC16 tumour. This suggests that fat may be able to overcome some of the metabolic defects seen in cancer cachexia.…”