Weight loss and metabolic alterations induced by recombinant tumour necrosis FACTOR-ALPHA (TNF)

Abstract

The weight loss and metabolic alterations induced by human recombinant tumour necrosis factor-alpha (TNF) in female NMRI mice were compared with those produced by a cachexia-inducing tumour (the MAC 16 adenocarcinoma), by a restricted food and water intake (pair-feeding), and by mitozolamide, a drug which in toxic doses produces anorexia and weight loss. Methods of reversing the TNF-induced weight loss, and the mechanisms involved in the weight reduction and the TNF-induced hypoglycaemia were investigated. The weight loss produced by a single injection of TNF was accompanied by anorexia and a decrease in the body water and carcass fat contents of mice. The TNF-induced weight loss was similar to that observed in mitozolamide­treated and pair-fed animals, and thus it appeared to be the result of anorexia. However, tolerance to the weight loss and anorectic effects of TNF occurred after the first injection. The MAC 16 tumour-induced weight loss occurred without anorexia and, in addition to a decline in body water and fat content, muscle catabolism was observed. No catabolic effects of TNF were demonstrated, but rather distinct anabolic actions. TNF was not shown to be produced by the MAC 16 tumour. TNF induced hypoglycaemia in mice, which was much more pronounced than that seen in MAC 16 tumour-bearing animals. This hypoglycaemia served to maintain ah elevated lipogenesis, primarily by the liver. The weight loss induced by TNF was reversed by rehydrating mice and by prior administration of indomethacin. Although TNF was shown to induce elevated levels of prostaglandin E2 (PgE2), and 16,16-dimethyl PgE2 caused weight loss in mice, PgE2 did not appear to be involved in the TNF-induced weight loss. In conclusion, the weight loss produced by TNF was the result of a direct anorectic and dehydrating effect of this agent, in contrast to the complex metabolic alterations observed in cancer cachexia.

Publication DOI: https://doi.org/10.48780/publications.aston.ac.uk.00012541
Divisions: College of Health & Life Sciences
Additional Information: © Susan Maria Mahony, 1989. Susan Maria Mahony asserts their moral right to be identified as the author of this thesis. This copy of the thesis has been supplied on condition that anyone who consults it is understood to recognise that its copyright rests with its author and that no quotation from the thesis and no information derived from it may be published without appropriate permission or acknowledgement. If you have discovered material in Aston Publications Explorer which is unlawful e.g. breaches copyright, (either yours or that of a third party) or any other law, including but not limited to those relating to patent, trademark, confidentiality, data protection, obscenity, defamation, libel, then please read our Takedown Policy and contact the service immediately.
Institution: Aston University
Uncontrolled Keywords: weight loss,metabolic alterations,recombinant tumour necrosis,FACTOR-ALPHA,TNF
Completed Date: 1989-04
Authors: Mahony, Susan M.

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