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Thermogenesis a key to pre-disposition for obesity

Professor Iain Clarke is overseeing a multi-pronged approach to physiology research. The head of the Department of Physiology, he has focused his department on several key pillars including neuroendocrinology, obesity, diabetes, cardiovascular/kidney disease and sensory and autonomic neuroscience. Iain's main area of research is neuroendocrinology, which relates to the interaction between the nervous and hormonal systems. He has recently made two discoveries that could change how we view fertility and obesity.




Iain is interested in how the brain and pituitary gland control reproduction, appetite and energy expenditure, and how this relates to obesity and fertility. With regard to the obesity issue, he believes we should be focussing on appetite.

'Three large studies involving thousands of people have been done around the world, where a program of diet and exercise was imposed,' Iain explains. 'Certainly, people lost weight on those programs, but as soon as it stopped, they went right back to where they were at the start. There's an inherent problem in trying to solve the obesity problem by controlling food intake; it just doesn't work. Everybody has a homeostatic set-point that is determined by the genes they inherited from their parents. Other factors can impact on that, but by and large it's genetic.'

Iain's solution to this problem is to focus on energy expenditure. The body breaks this down into various components, one of which thermogenesis. Iain believes this process is vital in determining whether an individual has a predisposition to obesity.

'Traditionally thermogenesis was thought to only exist in newborns, but we know now it exists in adults as well. After lunch you feel warm and drowsy because your temperature has risen through postprandial thermogenesis. We've shown that some individuals have very high postprandial thermogenesis and some have very low postprandial thermogenesis. Those with low levels become overweight and those with high levels do not. We can also apply a test and say 'you're going to become overweight and you're not', which is a major breakthrough. The next step is to find a way to manipulate heat production,' he says.

Iain has also identified peptides in the brain that have both positive and negative effects on reproduction. In collaboration with Dr Jeremy Smith, Iain is investigating the use of these agents in a range of situations of infertility and fertility. Iain is most excited by the gonadotropin-inhibitory hormone, which is also related to the issue of food intake.

'This peptide consists of only eight amino acids, but intravenous infusion can block ovulation. If you squirt it into the brain, it doubles food intake within two hours. It inhibits reproduction and stimulates food intake, so it could be a molecular switch in the brain. We know that food intake is lower in human females at the time of ovulation, and that's when the levels of these peptides are at their lowest. There's a reduction in the negative effect on reproduction that allows that to happen and a reduction in the stimulatory effect of feeding, which reduces appetite,' Iain explains.

Iain is also collaborating with Helen Truby from the Department of Nutrition and Dietetics and Shantha Rajaratnam from the School of Psychology and Psychiatry to create a translational physiology unit at Notting Hill. He says this facility will offer dynamic multi-disciplinary research opportunities.

'It puts a nutrition/dietetics kitchen beside a sleep lab and an exercise physiology lab. Those three areas will interact and the work will be done in humans. It will become operational in 2012 and I want to engage everyone to use it.'

Research area keywords

  • Neuroendocrinology
  • Reproduction
  • Metabolic Neuroscience
  • Large Animal Models
  • Hypothalamus

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Projects 2000 2017

Research Output 1973 2019

Brown adipose tissue thermogenesis in polycystic ovary syndrome

Shorakae, S., Jona, E., de Courten, B., Lambert, G. W., Lambert, E. A., Phillips, S. E., Clarke, I. J., Teede, H. J. & Henry, B. A., 1 Mar 2019, In : Clinical Endocrinology. 90, 3, p. 425-432 8 p.

Research output: Contribution to journalArticleResearchpeer-review

Lipopolysaccharide reduces gonadotrophin-releasing hormone (GnRH) gene expression: Role of RFamide-related peptide-3 and kisspeptin

Lee, C. Y., Li, S. Y., Li, X. F., Stalker, D. A. E., Cooke, C., Shao, B., Kelestimur, H., Henry, B. A., Conductier, G., O'Byrne, K. T. & Clarke, I. J., 29 Mar 2019, In : Reproduction, Fertility and Development. 31, 6, p. 1134-1143 10 p.

Research output: Contribution to journalArticleResearchpeer-review

Continuous kisspeptin restores luteinizing hormone pulsatility following cessation by a neurokinin b antagonist in female sheep

Clarke, I. J., Li, Q., Henry, B. A. & Millar, R. P., 1 Feb 2018, In : Endocrinology. 159, 2, p. 639-646 8 p.

Research output: Contribution to journalArticleResearchpeer-review

Exercise counteracts the homeostatic decrease in thermogenesis caused by caloric restriction in sheep

Fuller-Jackson, J-P., Clarke, I. J., Rao, A. & Henry, B. A., 1 Jul 2018, In : FASEB Journal. 32, 7, p. 3859-3869 11 p.

Research output: Contribution to journalArticleResearchpeer-review

Is centrally induced alveolar bone loss in a large animal model preventable by peripheral hormone substitution?

Simon, M. J. K., Beil, F. T., Pogoda, P., Vettorazzi, E., Clarke, I., Amling, M. & Oheim, R., Jan 2018, In : Clinical Oral Investigations. 22, 1, p. 495-503 9 p.

Research output: Contribution to journalArticleResearchpeer-review

Prizes

Ernst Knobil Lecture for 2013

Iain Clarke (Recipient), 2013

Prize: Prize (including medals and awards)

Geoffrey Harris Prize for 2013

Iain Clarke (Recipient), 2013

Prize: Prize (including medals and awards)

Honorary Degree of Doctor of Science

Iain Clarke (Recipient), 2013

Prize: Prize (including medals and awards)

The Geoffrey Harris Memorial Award

Iain Clarke (Recipient), 2010

Prize: Prize (including medals and awards)