Three researchers from the University of Copenhagen are the first to identify where in the body specific ‘obesity genes’ are active.
Why are some people susceptible to obesity while others seem to be able to maintain a so-called normal weight throughout their lives?
This question has perplexed scientists the world over, and there are many ideas as to the underlying cause of obesity development. As Tune H Person, Associate Professor and Lundbeck Foundation Fellow at the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, explains:
‘Some theories indicate that the explanation lies in the gut and its bacterial flora, others advocate the importance of the processes handled by fat cells. Each one of these theories could easily have valuable answers, but none build a coherent picture of the biochemical signalling circuits responsible for controlling development of obesity. And we’re now able to map the contours of this biological signalling,’ says Tune Pers.
Together with colleagues from the Center for Basic Metabolic Research, Pascal N. Timshel and Jonathan J Thompson, he recently published a research article in the scientific journal eLife.
‘And to cut a long story short, we proved that obesity is located in the brain. The studies on which our work is based clearly indicate that the genetics of obesity are primarily located in the brain,’ Tune Pers explains.
Obesity is rife
As the bathroom scales in most countries across the globe reveal, there is an obvious need to identify the key biological mechanisms underlying obesity. And the trend is consistently downwards:
Numbers published by the WHO show that the percentage of the world’s population who are either overweight or decidedly obese has steadily increased since 1975. Today, 13% of all adults in the world are clinically obese, and from a clinical point of view around 40% can be classed as overweight. In Denmark, these percentages are 17 ad 51, respectively.
‘So, obesity is rife. And if science is to offer effective treatments and prevention, we need to understand the genetic factors underlying the development of obesity and overweight,’ points out Tune Pers.
The research article in eLife discusses 700 genetic variants which, in numerous international studies of the entire human genome, have proven to be associated with obesity.
There is no doubt that these 700 genetic variants have a hand in controlling the development of obesity and overweight in some way or another. And, as Tune Pers explains, nor is there any doubt that a tendency to develop obesity is, to a large extent, hereditary in humans:
‘Up to now, we just haven’t been able to pinpoint where in the body – so, in which cells and tissue types – the 700 genetic variants are active in human beings. We decided to investigate, and we did this by looking at the results of rodent studies. Mice and humans are both mammals, and they have so many basic biological traits in common that it’s quite feasible to map the body’s cell types based on studies of mice.’
In the brain
Using a special technique able to track the signalling in all mammalian cell and tissue types, Tune Pers and his colleagues studied all of the 700 genetic variants associated with obesity in humans.
Although, in the field of obesity research, it is commonly believed that the genetics of obesity are linked to fatty tissue, the researchers at the University of Copenhagen also expected to find significant activity in the brain. Tune Pers explains:
‘But the remarkable thing was that all of the 700 genetic variants were only active in the brain – and nowhere else in the body.’
For example, the researchers could see that some of the variants emitted biochemical signals from the hypothalamus, an area of the brain containing a variety of cell types that are known to have an influence on obesity.
However, it turned out that the majority of the 700 genetic variants emitted biochemical signals from areas of the brain linked to memory and the ability to make decisions – or from areas that integrate sensory input.
In answer to the question of whether these findings could be used to design drugs or other therapies for treating obesity, Tune Pers says:
‘Not directly. Although we now know that the 700 obesity-related genetic variants are active in mammals’ brains – and nowhere else in their bodies – we still don’t have a full picture of their activity. What we do know now is where in the brain to look for more answers.’