Scientists in the UK have discovered that leptin, one of the hormones that regulates hunger and feeling full, controls our liking for food via a separate but linked pathway in the brain that also affects how much we eat. It is hoped that this discovery and more research will lead to greater understanding of the complex causes of obesity.
The study was funded by the Medical Research Council in the UK and the Wellcome Trust and is published in the early online issue of the journal Science.
The research was led by two scientists at Addenbrooke’s Hospital at the University of Cambridge: Dr Sadaf Farooqi from the Departments of Medicine and Clinical Biochemistry, and Dr Paul Fletcher from the Brain Mapping Unit in the Department of Psychiatry.
Eating behaviour is controlled by an interconnected complex of physiological, neural, cognitive and hormonal processes, each of which can be triggered by seeing, tasting, or even just thinking about food. In order better to understand what regulates eating behaviour, scientists have to unravel each process at a time and also try to find out how they work together.
For instance, although hunger affects what people eat and how much they eat, other factors are also involved. The act of eating is a pleasurable and rewarding experience in its own right, and a liking for food can override the biological cues that control feeling hungry and feeling full.
Farooqi, Fletcher and colleagues had a hunch that leptin, a hormone involved in controlling weight gain, played a role in the relationship between the process that controls feeling hungry and full and the process that generates feelings of pleasure and reward from the act of eating food.
Using imaging technology, Farooqi, Fletcher and colleagues showed that a liking for food has strong effects on the brain. When they scanned the brains of leptin deficient patients while they looked at images of food, they noticed activity in the brain regions responsible for emotions of reward and desire.
Leptin is made in fat cells and when it gets to the brain through the bloodstream it reduces feelings of hunger and increases feelings of fullness.
There are a very small number of people in the world who have a rare genetic disorder whereby their bodies can’t make leptin. These patients can’t stop eating, they like all foods equally, no matter how bland they are, and they become severely obese. When they are given leptin they find some foods tastier and more appetising than others and they begin to lose weight.
Two patients with the leptin deficiency disorder were invitied to look at images while their brains were being scanned using Functional Magnetic Resonance Imaging (fMRI). This technology shows which regions of the brain light up when a patient looks at an image. In this case the patients looked at pictures of food and pictures of objects that were not food such as cars and trees. Among the food images some were what one might classify as appetising such as cakes pizza and strawberries while others were what might be classed as bland (cauliflower and broccoli).
Then the patients were given leptin for 7 days and the experiment repeated.
Healthy volunteers were also invited to do the same: look at various images of non food items, appetising food and the same bland foods, and their brain scans were compared to the leptin deficient patient scans.
The leptin deficient patient brain scans showed that several parts of their brain, the striatal regions, responded to pictures of food. These are the areas of the brain involved in emotions of reward and desire. After they had been taking leptin for 7 days, the activity reduced when they looked at food pictures.
The scientists noticed that one brain region was particularly responsive to images of food that people generally find more appetising. This region was the nucleus accumbens. For instance it responds more to pictures of chocolate cake than it does to pictures of broccoli.
In the healthy volunteers, the nucleus accumbens only responded to appetising food when they were hungry (after fasting overnight).
In the leptin deficient patients, the nucleus accumbens showed the same high level of activity for appetising food both after following an overnight fast and after they had just eaten.
However, after taking leptin for 7 days, the nucleus accumbens of these patients became more like the healthy volunteers’: its highest activity for appetising food came only after the overnight fast, when they had had nothing to eat and were hungry. The activity after they had just eaten was reduced.
The scientists concluded there are two distinct pathways that interact: one controls hunger and fullness and the other is involved in liking and desiring food. Hunger evokes responses in the striatal region of the brain when images of food are seen, and eating changes these responses. It is the second process that is affected by the presence or lack of leptin. When leptin is missing, the striatal regions remain sensitive to cues of food, even after just eating a meal.
Commenting on their findings, Farooqi said:
“While body weight remains stable for many people over a long period of time, other people gain weight very easily. More studies are needed to find out how these brain responses vary in people with weight problems in general. Research is needed to find out how leptin triggers other chemicals in the brain and how alteration of these pathways contributes to overeating and obesity.”
He said more needs to be understood about how hormones that signal hunger and control energy stores interact in the brain and how this affects eating behaviour, and hopefully this will “take us beyond some of the prevailing and simplistic assumptions about why some people have difficulties in controlling how much they eat.”
“Such understanding will be a key step in the prevention and treatment of obesity. Importantly, the finding that the liking of food is biologically driven should encourage a more sympathetic attitude to people with weight problems,” she added.
“Leptin Regulates Striatal Regions and Human Eating Behavior.”
I. Sadaf Farooqi, Edward Bullmore, Julia Keogh, Jonathan Gillard, Stephen O’Rahilly, Paul C. Fletcher.
Science, Published Online August 9, 2007
Written by: Catharine Paddock