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Title: Metabolic characterisation of hypothalamic appetite pathways
Author: Semjonous, Nina M.
ISNI:       0000 0001 3393 6065
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2008
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The Comprehensive Laboratory Animal Monitoring System (CLAMS) is an automated cage system that allows continuous and simultaneous measurements of food intake, activity, oxygen consumption, carbon dioxide production and respiratory exchange ratio. In this thesis, I have developed and optimised the CLAMS as a tool for measuring metabolic parameters within the laboratory. I have then used this system to characterise the effect of a single ICV injection of hypothalamic neuropeptides involved in energy balance. I examined the effect of the orexigenic neuropeptides neuropeptide Y (NPY), agouti-related protein (AgRP), melanin concentrating hormone (MCH), orexin-A and ghrelin in satiated male Wistar rats, whilst the anorexigenic neuropeptides a-melanocyte stimulating hormone (a-MSH), corticotrophin-releasing hormone (CRH) and neuromedin U (NMU) were given to overnight fasted animals. Some peptides exhibited a co-ordinated metabolic response. For example, NPY and orexin-A both stimulated food intake but had opposing effects on energy expenditure. Among the anorectic peptides examined, CRH and NMU showed contrasting temporal effects on feeding and activity, despite the effects of NMU being though to occur via the release of CRH. These studies demonstrate that the CLAMS are a useful tool in determining the roles of well characterised peptides in energy balance. I then went on to use the CLAMS to aid in the' characterisation of the recently discovered . hypothalamic neuropeptide neuromedin S (NMS). Centrally, NMS is specifically expressed in the hypothalamic suprachiasmatic nucleus and is structurally similar to the neuropeptide NMU. Both peptides bind to the NMU1R and NMU2R with comparable affinities. I have used the CLAMS to characterise the effects of intrahypothalamic injection of NMS on food intake, activity and energy expenditure. NMS dose dependently reduced food intake more potently than NMU. This inhibition of feeding was associated with an increase in stress-related behaviours, such as grooming. Microinjection of NMS directly into the PVN also activated the HPA axis at a similar magnitude to NMU, as demonstrated by elevated plasma ACTH and corticosterone. This work suggests that NMS may be involved in the regulation of energy homeostasis and the stress response.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available