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 Obesity and Metabolic Health Programme
 - Molecular Endocrinology Group

Identification of genes important for the regulation of energy balance - Dr. Kanishka Nilaweera

Areas of Research

• Analysis of gene expression in animal models of altered energy balance

• Identification of molecular mechanisms of body weight regulation, particularly in relation to histamine signalling

Although the discovery of hormones such as leptin and ghrelin and neuropeptides such as pro-opiomelanocortin and neuropeptide Y, and their cognate receptors, has greatly increased our understanding of how body weight is regulated in humans, the interactions between these proteins, especially in the hypothalamic nuclei, alone cannot account for the degree of regulation required to achieve energy homeostasis in a background of constant changing energy intake and energy expenditure in humans. This study therefore aims to identify novel genes expressed in the hypothalamus that are important for the regulation of energy balance. To this end, the techniques of laser capture microdissection and microarrays have been utilised to identify genes that show changes in their expression in hypothalamic nuclei of interest in relation to altered energy levels, such as that exhibited by the Siberian hamsters exposed to different photoperiods (short or long days). Genes of interest that are identified will be investigated further utilising a range of molecular biology techniques including in situ hybridisation to determine how the protein products of these genes could contribute to energy homeostasis in Siberian hamsters as well as in other rodents such as mice and rats.

In parallel with these studies, the present study also aims to further explore a recent finding by our group that the histamine signalling through H3 receptor in the posterior part of the hypothalamus, tentatively called the dmpARC, is important for the regulation of body weight in Siberian hamsters. Through collaborative work with Nottingham University in UK, we are attempting to understand the molecular mechanisms by which histamine could regulate energy balance in these animals.

Recent Publications

Jethwa PH, Warner A, Nilaweera KN, Brameld JM, Keyte JW, Carter WG, Bolton N, Bruggraber M, Morgan PJ, Barrett P, Ebling FJ. VGF-derived peptide, TLQP-21, regulates food intake and body weight in Siberian hamsters, Endocrinology. 2007 Apr 26;

Mercer JG, Archer ZA, Barrett P, Nilaweera KN, Ross AW, Morgan PJ. Circadian and circannual effects on energy balance circuits in the Siberian hamster. Progress in Obesity Research 10, ISBN 978-0-646-47086-3 and ISO106

Nilaweera KN, Ozanne D, Wilson D, Mercer JG, Morgan PJ, Barrett P. G protein-coupled receptor 101 mRNA expression in the mouse brain: altered expression in the posterior hypothalamus and amygdala by energetic challenges, J Neuroendocrinol. 2007 Jan;19(1):34-45

Graham, E.S., Turnbull, Y., Fotheringham, P., Nilaweera, KN., Mercer, J.G., Morgan, P.J., & Barrett, P. (2003). Neuromedin U and Neuromedin U receptor-2 expression in the mouse and rat hypothalamus: effects of nutritional status. J. Neurochem., 87, 1165-1173.

Nilaweera, K. N., Barrett, P., Mercer, J. G., & Morgan, P. J. (2003). Precursor-protein convertase 1 gene expression in the mouse hypothalamus; differential regulation by the ob gene mutation, energy deficit and administration of leptin, and coexpression with prepro-orexin. Neurosci., 119, 713-720.

Nilaweera, K. N., Ellis, C., Barrett, P., Mercer, J. G., & Morgan, P. J. (2002). Hypothalamic bHLH transcription factors are novel candidates in the regulation of energy balance. Eur J Neurosci, 15, 644-650.

Full RRI publication List

Contact details for Dr. Kanishka Nilaweera

Email: K.Nilaweera@rowett.ac.uk

Telephone:+44 (0)1224 712751 Ext.2486