Leptin, already identified as a key hormone responsible for reducing hunger and increasing the feeling of fullness, has now also been found to control whether or not people find foods appetising. According to the team of researchers from the University of Cambridge in the UK, this is what leads to overeating, as it overrides the biological cues that govern hunger and fullness. Headed by Dr Sadaf Farooqi and Dr Paul Fletcher, the researchers studied patients with a rare genetic disorder resulting in a complete lack of leptin. These patients eat excessively, like all types of food (including bland foods) and develop severe obesity. In the study, which was published in the journal Science on August 9, the patients were asked to look at a series of pictures while brain activity was recorded using Functional Magnetic Resonance Imaging (fMRI). The fMRI scanner shows which parts of the brain are activated or 'light up' in response to different pictures. The pattern of brain activation in response to pictures of food was compared to that seen with pictures of non-food items such as trees, cars, and boats. Some of the foods were appetising (chocolate cake, strawberries, pizza) while others were bland (cauliflower, broccoli). The authors showed that in the patients lacking leptin, several areas of the brain - known collectively as striatal regions - responded to pictures of food. When the patients were treated with leptin, responses to food pictures in these areas were reduced. At the same time, hunger was reduced, and patients became more choosey about food - ultimately resulting in weight loss. According to the study, one of the striatal regions - the nucleus accumbens - was especially responsive to pictures of food that people found appetising. In healthy volunteers, activation of the nucleus accumbens by appetizing foods was only found when the person was hungry (following an overnight fast). In the leptin deficient patients, the nucleus accumbens was activated when patients were hungry, but also after they had just eaten. After treatment with leptin, the response in these patients normalised so that the nucleus accumbens was activated predominantly by foods they liked and only when they had had nothing to eat overnight and were hungry. The scientists said their findings have important implications for the understanding of how two key systems - the pathways that control hunger and fullness and the brain processes involved in liking and wanting foods - may interact. "Hunger clearly has an impact on activation in striatal regions of the brain in response to food pictures and consumption of food modifies these responses. This modification requires the hormone leptin since, when it is lacking, these brain regions remain very sensitive to the presence and type of food pictures even following a meal." According to Dr Farooqi, while body weight remains stable for many people over a long period of time, other people gain weight very easily. She suggested 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, " she said. "Understanding how brain systems interact with hormones that signal hunger and energy stores will provide us with a more complete picture of factors controlling eating behaviour and will hopefully 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."