ENERGY METABOLISM IN CACHECTIC TUMOUR BEARING RATS

Omar  A.  OBEID

Cachexia is a common finding among cancer patients and contributes to a large proportion of deaths. The mechanism(s) by which cancer induces cachexia is not yet clear.

A Leydig cell tumor was used to investigate some aspects of cachexia. Tumor growth in Fischer rats was found to be a good models of cachexia, by exhibiting the same characteristics as human cancer chachexia e.g. anorexia and weight loss. However tumor growth in Sprawgue Dawley (SD) rats was inconsistent in the take of tumor and in the effect of tumor growth between animals. Moreover, the effect of tumor growth in SD rats did not show the same characteristics as that of Fischer rats in many aspects e.g. food intake of tumor bearing (TB) Fischer rats was decreased by about 40%, while that of TB SD rats was decreased by about 9 %. Also, energy expenditure of TB Fisher rats was decreased compared with ad lib fed controls, while that of TB SD rats was increased. Therefore Fischer rats were used in all subsequent experiments.

Experiments utilizing Skinner boxes showed that the anorexia of TB rats was caused mainly by reduced hunger rather than early satiety.

Comparison with pair fed controls showed that anorexia did not account for all the wasting in TB rats, and energy expenditure was increased.

Leydig cell tumors produce testosterone, but injections of testosterone in normal rats did not cause the same wasting as tumor growth.

The rate of hepatic glycogen synthesis in response to a meal was found to be higher and maintained for a longer time in TB rats compared with control rats.

Lipogenesis in TB rats was found to be depressed in the (ad lib) fed state. This depression was caused mainly by decreased food intake. Adipose tissue of TB rats did not show the normal increase in lipogenic activity in response to a meal.

Adipose tissue lipoprotein lipase (LPL) activity of 24 hr fasted TB rats was normal, but showed a blunted response to feeding. In contrast, tumor lipogenic and LPL activity was maintained during tumor growth and was not affected b y the nutritional state of the host.

The present experimental investigation suggests that tumor growth results in alteration in the metabolic flux following a meal, by directing metablolites towards glycogen synthesis rather than fatty acid synthesis. Also, many of the observations could be explained by delayed stomach emptying. These alterations in metabolic flux may be involved in the regulation of food intake in TB rats