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The brain’s appetite control centre is different in the brains of people who are overweight or live with obesity, a new study suggests. The researchers said their findings add further evidence to the relevance of brain structure to weight and food consumption. Current estimates suggest that more than 1.9 billion people worldwide are either overweight or obese. And, according to the Office for Health Improvement and Disparities, almost two-thirds of adults in the UK are overweight or living with obesity. This increases the risk of developing health issues like type 2 diabetes, heart disease and stroke, cancer and poorer mental health. The last two decades have given us important insights about appetite control and how it may be altered in obesity Professor Paul Fletcher, University of Cambridge A number of factors influence how much people eat and what they eat, including genetics, hormone regulation, and the environment they live in, researchers say. However, it is not entirely clear what happens to the brain to tell us that we are hungry or full. Past studies have shown that the hypothalamus – a small region of the brain about the size of an almond – plays an important role. Dr Stephanie Brown, from the Department of Psychiatry and Lucy Cavendish College, University of Cambridge, said: “Although we know the hypothalamus is important for determining how much we eat, we actually have very little direct information about this brain region in living humans. “That’s because it is very small and hard to make out on traditional MRI brain scans.” Professor Paul Fletcher, the study’s senior author, from the Department of Psychiatry and Clare College, Cambridge, said: “The last two decades have given us important insights about appetite control and how it may be altered in obesity. “Metabolic researchers at Cambridge have played a leading role in this. “Our hope is that, by taking this new approach to analysing brain scans in large datasets, we can further extend this work into humans, ultimately relating these subtle structural brain findings to changes in appetite and eating and generating a more comprehensive understanding of obesity.” The majority of evidence for the role of the hypothalamus in appetite regulation comes from animal studies, which indicate complex interacting pathways within the hypothalamus, with different cell populations acting together to tell us when we are hungry or full. To get around this researchers used an algorithm developed using machine learning to analyse brain scans taken from 1,351 young adults across a range of BMI scores. They looked for differences in the hypothalamus when comparing individuals who are underweight, healthy weight, overweight, or living with obesity. According to the findings, the overall volume of the hypothalamus was significantly larger in the overweight and obese groups of young adults. The researchers describe a significant relationship between volume of the hypothalamus and body mass index (BMI). The differences were most apparent in those sub-regions of the hypothalamus that control appetite through the release of hormones to balance hunger and fullness. While the exact significance of the finding is unclear, one explanation is that the change relates to inflammation, the researchers suggest. Eating a high-fat diet could trigger inflammation of our appetite control centre Dr Stephanie Brown, University of Cambridge Previous animal studies have shown that a high-fat diet can cause inflammation of the hypothalamus, which in turn prompts insulin resistance and obesity. In mice, just three days of a fat-rich diet is enough to cause this inflammation. Other studies have shown that this inflammation can raise the threshold at which animals are full – in other words, they have to eat more food than usual to feel full. Dr Brown added: “If what we see in mice is the case in people, then eating a high-fat diet could trigger inflammation of our appetite control centre. “Over time, this would change our ability to tell when we’ve eaten enough and to how our body processes blood sugar, leading us to put on weight.” More research is needed to confirm whether increased volume in the hypothalamus is a result of being overweight or whether people with larger hypothalami are predisposed to eat more in the first place. It is also possible that these two factors interact with each other, causing a feedback loop, the study published in Neuroimage: Clinical, and supported by the Bernard Wolfe Health Neuroscience Fund, Wellcome and the NIHR Cambridge Biomedical Research Centre, with additional funding from Alzheimer’s Research UK, suggests.

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