Brain's 'appetite control center' different in people who are overweight or living with obesity

Cambridge scientists have shown that the hypothalamus, a key region of the brain involved in controlling appetite, is different in the brains of people who are overweight and people with obesity when compared to people who are a healthy weight.

The researchers say their findings add further evidence to the relevance of brain structure to weight and food consumption.

Current estimations suggest that over 1.9 billion people worldwide are either overweight or obese. In the UK, according to the Office for Health Improvement & Disparities, almost two-thirds of adults are overweight or living with obesity. This increases an individual's risk of developing a number of health problems, including type 2 diabetes, heart disease and stroke, cancer and poorer mental health.

A large number of factors influence how much we eat and the types of food we eat, including our genetics, hormone regulation, and the environment in which we live. What happens in our brains to tell us that we are hungry or full is not entirely clear, though 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."

The majority of evidence for the role of the hypothalamus in appetite regulation comes from animal studies. These show that there are 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, Dr Brown and colleagues used an algorithm developed using machine learning to analyse MRI brain scans taken from 1,351 young adults across a range of BMI scores, looking for differences in the hypothalamus when comparing individuals who are underweight, healthy weight, overweight and living with obesity.

In a study published today in Neuroimage: Clinical, the team found that the overall volume of the hypothalamus was significantly larger in the overweight and obese groups of young adults. In fact, the team found a significant relationship between volume of the hypothalamus and body-mass index (BMI).

These volume 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 precise significance of the finding is unclear -- including whether the structural changes are a cause or a consequence of the changes in body weight -- one possibility is that the change relates to inflammation. 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, the study's first author, 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."

Inflammation may explain why the hypothalamus is larger in these individuals, the team say. One suggestion is that the body reacts to inflammation by increasing the size of the brain's specialist immune cells, known as glia.

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 team say 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.

Read more at Science Daily

Sweet taste reduces appetite?

 The sweet taste of sugar is very popular worldwide. In Austria and Germany, the yearly intake per person adds up to about 33 and 34 kilograms, respectively. Thus, sugar plays an increasingly role in the nutrition and health of the population, especially with regard to body weight. However, little is known about the molecular (taste) mechanisms of sugar that influence dietary intake, independently of its caloric load.

Taste receptor and satiety regulation

"We therefore investigated the role of sweet taste receptor activation in the regulation of satiety," says Veronika Somoza, deputy head of the Department of Physiological Chemistry at the University of Vienna and director of the Leibniz Institute for Food Systems Biology at the Technical University of Munich.

For this purpose, the scientists conducted a blinded, cross-over intervention study with glucose and sucrose. A total of 27 healthy, male persons, between 18 and 45 years of age, received either a 10 percent glucose or sucrose solution (weight percent) or one of the sugar solutions supplemented with 60 ppm lactisole. Lactisole is a substance that binds to a subunit of the sweet receptor and reduces the perception of sweet taste. Despite different types of sugar, all solutions with or without lactisole had the same energy content.

Two hours after drinking each of the test solutions, the participants were allowed to have as much as breakfast they wanted. Shortly before and during the 120-min waiting period, the researchers took blood samples in regular intervals and measured their body temperature.

Additional 100 kilocalories on average

After the consumption of the lactisole-containing sucrose solution, the test persons had an increased energy intake from breakfast of about 13 percent, about 100 kilocalories more, than after drinking the sucrose solution without lactisole. In addition, the subjects of this group showed lower body temperature and reduced plasma serotonin concentrations. Serotonin is a neurotransmitter and tissue hormone which, among other things, has an appetite-suppressing effect. In contrast, the researchers observed no differences after administration of the lactisole-containing glucose solution and the pure glucose solution.

"This result suggests that sucrose, regardless of its energy content, modulates the regulation of satiety and energy intake via the sweet taste receptor," says Barbara Lieder, head of Christian Doppler Laboratory for Taste Research and also deputy head of the Department of Physiological Chemistry of the Faculty of Chemistry at University of Vienna.

The first study author of the study, Kerstin Schweiger, University of Vienna adds: "We do not know yet why we could not observe the lactisole effect with glucose. However, we suspect it is because glucose and sucrose activate the sweet receptor in different ways. We also assume that mechanisms independent of the sweet receptor play a role."

Read more at Science Daily