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Brain scans reveal circuits that control food intake

OCTOBER 15, 2007

The Centre for Neuro-Imaging at King's and colleagues from University College London (UCL) have identified the circuits that ‘decide' how much people eat. Using live brain scanning techniques and an innovative design study, researchers have discovered how the brain controls food intake in humans. The findings are published this week in Nature.

The group of scientists from UCL and King's used peptide YY (PYY), a naturally occurring hormone that regulates appetite, to investigate which areas of the brain are involved in controlling food intake. Studies in animals had suggested that PYY acted on the homeostatic regions of the brain (hypothalamus and brainstem), which govern primitive functions. However, there was no information on how this hormone regulates eating in humans.

This latest research was led by Dr Rachel Batterham at UCL, involved Professor Steve Williams and his team at the Centre for Neuro-imaging Services based at the Institute of Psychiatry where brain scanning and analysis of the research were carried out. Researchers used functional Magnetic Resonance Imaging (fMRI) and found that PYY not only targets the primitive homeostatic parts of the brain that control feeding but also acts in the cortico-limbic brain regions that determine the rewarding and pleasurable aspects of eating.

Dr Batterham, based at UCL, said: 'We were surprised to discover that the greatest change in brain activity in response to PYY was within the orbito frontal cortex (OFC), a region thought to act as an integrative hub and implicated in reward processing. More surprisingly we found that the change in OFC activity predicted how much food the volunteers subsequently ate. The greater the change in activity in that area, the less the subjects ate.'

Eight normal weight men took part in a double blind placebo-controlled study. After 14 hours without food subjects were given an intravenous drip of either PYY or placebo for 100 minutes while their brain was scanned continuously. Thirty minutes later they were offered an unlimited meal. Each subject was tested twice one week apart, once with PYY and once with the placebo in a random order. PYY infusion reduced food consumption in all 8 subjects and on average caused a 25% reduction in the calories eaten.

Dr Batterham explains 'In the food-deprived state brain activity within the hypothalamus predicted how much food the subjects ate. However, in the presence of increased PYY levels, mimicking a meal, there was a switch in the circuits controlling eating so that brain activity within the orbitofrontal cortex now predicted feeding behaviour.'

It is hoped studies using fMRI-based physiological approaches may help determine whether pharmacological or other interventions target appetite regulating regions.

Dr Batterham added: 'The obesity crisis continues unabated with 23% of the UK adult population and 33% of the US adult population now classified as obese. Whilst we know that body weight is determined by a balance between food intake and energy expenditure a clearer understanding of the brain circuits that regulate these processes could allow us to tackle one of the biggest health burdens western societies face today.'

Dr Batterham concludes that: 'Our study provides insights into how biological signals affect not only how full we feel but also the enjoyment of eating and may determine whether we reach for a second helping or are satisfied with the first. Understanding which brain regions control eating in different environmental conditions may help us to develop more targeted treatments for people with weight problems. Further research is now needed to investigate whether underweight and overweight people have abnormalities in these circuits'.

Professor Steve Williams, at the Centre for Neuro-Imaging at King's expanded further 'We hope that this research will also whet the appetite of psychiatrists whose interests range from eating disorders and obesity to issues of weight management in schizophrenia.'

Notes to editors
1. PYY modulation of cortical and hypothalamic brain areas predicts feeding behaviour in humans. Rachel L. Batterham, Dominic H. ffytche, J. Miranda Rosenthal, Fernando O. Zelaya, Gareth J. Barker, Dominic J. Withers & Steven C.R. Williams. Nature, aop, 18:00 14 October 2007.

2. Peptide YY (PYY) is a naturally occurring hormone which is released from the gut into the bloodstream after eating and signals to the brain that food has been eaten. Injections of this hormone have been shown to decrease food intake in normal and obese volunteers. Studies in laboratory animals have suggested that PYY regulates appetite by acting in primitive parts of the brain (hypothalamus and brainstem).

3. 8 male normal weight volunteers took part in a double blind placebo controlled study. Each volunteer was studied twice, once with PYY and once with placebo (saline), given in a random order one week apart. Prior to the start of the scanning session volunteers fasted for 14 hours. Subjects were given an infusion (placed on intravenous drip) of either PYY or placebo while their brain was scanned continuously for 100 minutes to assess brain activity. Thirty minutes after the end of the infusion, where the volunteers did not know if they were receiving PYY or placebo, they were offered an unlimited meal. PYY infusion reduced food in all 8 subjects and on average caused a 25% reduction in the calories eaten.

4. The research was undertaken as part of on ongoing programme at UCL investigating how body weight is controlled. UCL and UCLH have recently established a new centre to treat obese people and also undertake research into appetite regulation. The study was funded by the Medical Research Council and the Rosetrees Trust.
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