Abstract

Both urine and plasma from mice and humans with cancer cachexia have been shown to contain higher levels of lipid mobilising activity than normal controls, even after acute starvation. There was no significant increase in the urinary lipid mobilising activity of either mice or humans after acute starvation, suggesting that the material in the cachectic situation was probably not due to an elevation of hormones normally associated with the catabolic state in starvation. Further characterisation of the lipid mobilising activity in the urine of cachectic mice using Sephadex G50 exclusion chromatography showed four distinct peaks of activity of apparent molecular weights of greater than 20, 3, 1.5 and less than 0.7 kDa. No comparable peaks of activity were found in the urine of a non tumour-bearing mouse. The high molecular weight activity was probably formed by aggregation of low molecular weight material, since treatment with 0.5 M NaCl caused dissociation to material with a broad spectrum of molecular weights between 3 and 0.7 kDa. Lipolytic species of similar molecular weights were also found in the urine of cachectic cancer patients, but not in normal urine even after 24 h starvation. The lipid mobilising species may be responsible for catabolism of host adipose tissue in the cachectic state.

Highlights

  • With the presence of circulatory catabolic factors capable of breaking down both muscle and adipose tissue in vitro (Beck & Tisdale, 1987)

  • Similar elevations in lipid mobilising activity have recently been found in the serum and urine of patients with clinical cancer cachexia (Groundwater et al, 1990) and this study attempts to further characterise this activity

  • Despite the fact that animals bearing the MAC16 tumour have a food and water intake not significantly different from non tumour-bearing controls, weight loss is observed, which increases as the tumour burden increases (Table I)

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Summary

Methods

Pure strain NMRI mice were bred in our own colony. They were fed a rat and mouse breeding diet (Pilsbury, Birmingham, UK) and water ad libitum. Later studies reported a lipid mobilising factor present in both the serum of mice bearing a thymic lymphoma and a patient with advanced cancer (Kitada et al, 1981). The molecular weight of the material initially reported was 5 kDa, similar to that described in the present report, later studies (Kitada et al, 1982) suggested that activation only occurred on standing to give a high molecular weight material. Another lipid mobilising factor, Toxohormone L, has been isolated from the cell-free fluid of ascites sarcoma 180 and has been shown

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