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.

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The surprising science behind long-distance bird migration

A team of scientists led by researchers at the University of Massachusetts Amherst has recently made a surprising discovery, with the help of a wind tunnel and a flock of birds. Songbirds, many of which make twice-yearly, non-stop flights of more than 1,000 miles to get from breeding range to wintering range, fuel themselves by burning lots of fat and a surprising amount of the protein making up lean body mass, including muscle, early in the flight. This flips the conventional wisdom on its head, which had assumed that migrating birds only ramped up protein consumption at the very end of their journeys, because they would need to use every ounce of muscle for wing-flapping, not fuel. The results appeared recently in the Proceedings of the National Academy of Sciences.

"Birds are amazing animals," says Cory Elowe, the paper's lead author and a postdoctoral researcher in biology at UMass Amherst, where he received his Ph.D. "They are extreme endurance athletes; a bird that weighs half an ounce can fly, non-stop, flapping for 100 hours at a time, from Canada to South America. How is this possible? How do they fuel their flight?"

For a very long time, biologists assumed that birds fueled such feats of endurance by burning fat reserves. And indeed, fat is an important part of migratory birds' secret mix. "The birds in our tests burned fat at a consistent rate throughout their flights," says Elowe. "But we also found that they burn protein at an extremely high rate very early in their flights, and that the rate at which they burn protein tapers off as the duration of the flight increases."

"This is a new insight," says Alexander Gerson, associate professor of biology at UMass Amherst and the paper's senior author. "No one has been able to measure protein burn to this extent in birds before."

"We knew that birds burned protein, but not at this rate, and not so early in their flights," continues Gerson. "What's more, these small songbirds can burn 20% of their muscle mass and then build it all back in a matter of days."

To make this breakthrough, Elowe had help from the bird banding operators at Long Point Bird Observatory, in Ontario, along the northern shore of Lake Erie. Every fall, millions of birds gather near the observatory on their journey to their wintering grounds -- including the blackpoll warbler, a small songbird that travels thousands of miles during its migration. After capturing 20 blackpolls and 44 yellow-rumped warblers -- a shorter distance migrant -- using mist nets, Elowe and his colleagues then transported the birds to the Advanced Facility for Avian Research at Western University, which has a specialized wind tunnel built specifically for observing birds in flight.

Elowe measured the birds' fat and lean body mass pre-flight, then, when the sun set, let the birds free in the wind tunnel. Because the birds naturally migrate at night, Elowe and his colleagues would then stay awake -- at one point, for 28 hours -- watching for when a bird would decide to rest. At that point, the researchers would collect the bird and again measure its fat and lean body mass content, comparing them with the pre-flight measurements.

"One of the biggest surprises was that every bird still had plenty of fat left when it chose to end its flight," says Elowe. "But their muscles were emaciated. Protein, not fat, seems to be a limiting factor in determining how far birds can fly."

The researchers still don't quite know why the birds are burning such vast stores of protein so early in their journeys, but the possible answers open up a wide range of future research avenues.

"How exactly is it possible to burn up your muscles and internal organs, and then rebuild them as quickly as these birds do," wonders Gerson. "What insights into the evolution of metabolism might these birds yield?"

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