Trypanosoma brucei is the vector of African trypanosomiasis in both domestic animals (nagana) and sleeping sickness in humans (Human African Trypanosomiasis). These protozoan parasites are transmitted by the bite of infected tsetse flies (Glossina sp.). African trypanosome infections cause parasite-induced anorexia (PIA) and cachexia in livestock, experimental animals and in humans, and are of economic, veterinary and medical importance in sub-Saharan Africa. The overall aim of this project was to characterise the phenomenon of inappetence in relation to overall energy budget in African trypanosome infection and to then identify potential causal factors and mechanisms. A mouse model of T.b. brucei infection was established with a reproducible time course for the development of inappetence and bodyweight loss. Following an initial parasitaemic peak on day 6 post-infection, a profound period of inappetence was observed from days 7 to 11, accompanied by a 10% loss of body mass. Metabolisable energy intake was reduced, while assimilation efficiency increased significantly but not enough to compensate for the severe reduction in food intake. During the course of T.b. brucei infection, both total energy expenditure and physical activity were reduced. Although physical activity was markedly declined in both light and dark phases, trypanosome infected mice maintained their circadian rhythm albeit at a lower amplitude, with most of the activity occurring at the start of the dark phase. Resting metabolic rate was unchanged in infection. Plasma concentrations of the inflammatory cytokines, IL-6 and TNF-α were increased in infected mice and were associated with inappetence. Reductions of leptin and insulin concentration corresponded to a loss in fat mass. The hypothalamic control of appetite appeared to be normal with increases in appetite stimulating AgRP, decreases in the appetite inhibiting POMC and MC4R. There has been no previous data published on the control of appetite and energy expenditure in African trypanosome infections thus the data presented here provides a novel insight into the pathophysiology of this serious disease, and may lead to new therapies to manage the clinical and veterinary consequences of trypanosome infection.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:690574 |
| Date | January 2015 |
| Creators | Silva, Achani Madushika |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=230060 |
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