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The effect of cancer cachexia on the TAG/FA substrate cycle in white adipose tissue was determined in vivo using the MAC16 murine model of cachexia. When compared with non-tumor-bearing animals, the rate of TAG-glycerol production was found to be increased almost threefold in animals bearing the MAC13 tumor, which does not induce cachexia, but was not further elevated in animals bearing the MAC16 tumor. In both cases TAG-glycerol production and de novo synthesis of TAG-FA were also increased above non-tumor-bearing animals. In animals bearing the MAC16 tumor, the TAG-FA rates were significantly higher than in animals bearing the MAC13 tumor. This suggests that the presence of the tumor alone is sufficient to cause an increase in cycling rate, and in the absence of an elevated energy intake (MAC16) this may contribute to the depletion of adipose tissue.

Summary A comparison has been made of the cachectic effects produced by the transplantable murine adenocarcinoma of the mouse colon (MAC16) with tumour necrosis factor-a (cachectin). Tumour necrosis factor-a (TNF-a) produced a dose-related weight reduction that was accompanied by a decrease in both food and water intake. The degree of weight loss was directly proportional to the decreased food and water intake. In contrast weight loss produced by the MAC16 tumour occurred without a reduction in fluid or nutrient intake. Both the MAC16 tumour and TNF-a produced hypoglycaemia and a reduction in the circulatory level of free fatty acids (FFA), but had opposite effects on the level of plasma triglycerides with the MAC16 tumour-induced cachexia causing a decrease and TNF-a producing an increase. The MAC16 tumour elaborated a lipolytic factor which caused an immediate release of FFA from adipose tissue. In contrast TNF-a had no effect on mobilization of adipose triglycerides over a short time period. Both TNF-a and extracts from the MAC16 tumour caused an enhanced release of amino acids from mouse diaphragm, which was suppressible with indomethacin and heat labile. No TNF was detected in the MAC16 tumour or in the serum of tumour-bearing animals. Both tumour and non-tumour-bearing animals responded with a similar elevation of their serum TNF levels 90min after a single injection of endotoxin. It is concluded that weight loss produced by TNF-a arises from an anorexic effect and that this differs from the complex metabolic changes associated with cancer cachexia.We have been investigating a chemically induced, transplantable adenocarcinoma of the colon (MAC 16), passaged in inbred NMRI mice as an experimental model of cachexia (Bibby et al., 1987). This tumour produces weight loss at small tumour burdens (<1% of the host wcight) and without a reduction in the intake of either food or water. The weight loss, which is directly proportional to the tumour weight, is associated with a decrease in both carcass fat and muscle dry weight (Beck & Tisdale, 1987). The cachectic effect of the tumour has been attributed to the production of both lipolytic and proteolytic factors, which are present in the circulation of tumour-bearing animals.Endotoxin-induced cells of the reticuloendothelial system have been shown to elaborate a mediator called cachectin (tumour necrosis factor, TNF), which induces a state of cachexia in recipient animals . When chronically secreted by host macrophages cachectin has been suggested to contribute to a catabolic state, which ultimately leads to cachexia (Beutler & Cerami, 1986

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