Cachexia in experimental models

Cachexia refers to a state of severe malnutrition characterized by anorexia , weight loss, and muscle wasting. Although it is most commonly considered in the context of cancer, it may occur as a consequence of a variety of chr onic diseases. Cachexia appears to differ from "semistarvation" in that the re is evidence of metabolic changes that are different from the normal resp onse to reduced food intake. Animal models are useful in the study of cache xia because they allow homogeneous groups of subjects, free from confoundin g influences, to be studied. Accurate control of diet is possible, and pair -fed controls can be used to allow specific investigation of the metabolic component. However, the model muse show features that are appropriate for t he disease being studied. In the case of cancer this means using a model in which cachexia occurs without too high a tumor burden or growth rate or to o severe a reduction in food intake. Studies in the author's laboratory hav e used a transplantable Leydig cell tumor in Fischer rats. Food intake decr eases by 20-40% and energy expenditure is greater than that of pair-fed con trols. One mechanism that may be responsible for this relates to the postpr andial metabolism of carbohydrate, since after a test meal there appears to be a greater rate of hepatic glycogen synthesis via the indirect pathway i n tumor-bearing rats than in controls. The indirect pathway involves glucon eogenic enzymes, and studies using a variety of different tracers and enzym e inhibitors suggest that amino acids are important precursors. An increase d rate of hepatic glycogen synthesis also appears to be maintained for a lo nger time after the meal in tumor-bearing rats, and this may act to delay t he onset of the next meal, thereby explaining the decreased meal frequency that has been observed. (C) Elsevier Science Inc.