A complex combination appears to control appetite
The Nature study, by University College London and King's College London, could aid development of new obesity drugs.
Using brain scans, the teams showed the appetite-regulating hormone peptide YY (PYY) produces a more complex pattern of activity in the brain than thought.
It targets not only the primitive areas controlling basic hunger urges, but also the pleasure and reward centres.
PYY is released from the gut into the bloodstream after eating and signals to the brain that food has been eaten.
A nasal spray containing the hormone is currently being trialled to see if it can be used to tackle obesity.
Studies on animals suggest it regulates appetite by acting in primitive parts of the brain such as the hypothalamus and brainstem.
The latest study showed that the same was true in humans.
But the hormone was also found to act in the cortico-limbic regions that determine the pleasure sensations associated with eating food.
The biggest effect of all was found in an area called the orbitofrontal cortex (OFC) - a region thought to make overall sense of the pleasure sensation.
The researchers found that the greater the change in activity in that area, the less the volunteers ate.
Eight normal-weight men took part in the study. After 14 hours without food, they were given a drip of either PYY or a placebo for 100 minutes while their brains were scanned using an MRI machine.
Thirty minutes later they were offered an unlimited meal.
Each volunteer was tested twice, a week apart, once with PYY and once with the placebo.
PYY infusion reduced subsequent average calorific intake by 25%.
Researcher Dr Rachel Batterham, who is funded by the Medical Research Council, said: "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."
The researchers hope a greater understanding of how appetite is controlled could help tackle the obesity crisis - 23% of the adult UK population is classified as obese.
Dr Batterham said: "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."
Dr Ian Campbell, medical director of the charity Weight Concern, said weight control was not as simple as just counting calories.
He said: "Understanding the way we perceive food, develop the feeling of satiety, and our emotional relationship with food are key to helping an individual to regain control
"What this study seems to do is shed new light on one of the reasons why it's so difficult - more than just a behavioural issue, there may well be complex hormones that influence both the way we think and feel about the food we eat."
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