Marc Schneeberger Pané (Lloret, 1987) is young. He is only 36 years old. But despite this, he already runs his own research laboratory at Yale University (USA). With a degree in Pharmacy from UB, he went to New York to do a postdoc with the prestigious researcher Jeffrey Friedman, with whom he worked for seven years. Both found a new neural circuit that regulates hunger. This is the field of knowledge that makes you lose sleep. “My central question has always been how body weight is regulated,” he admits. His investigations have now earned him the Princess of Girona award for scientific research.
With Friedman, he was investigating brain circuits and is now focused on neurovasculature. What is it about?
We observed in obese mice that there are regions of the brain where neurons are more active. The latter, to function, need the bloodstream to transport oxygen and nutrients to the region of interest, but if they are active, they need it even more, so the blood supply has to increase. There was a dogma that said that the intensity of the irrigation could change, but not the structure of the cerebral vasculature (group of blood vessels).
And have they been able to refute it?
Yes. We created a technology that has allowed us to record the entire cerebral vasculature in three dimensions. We applied it to mice (some were thin and others obese) and we saw that the structure changed. There are small changes in certain regions functionally involved with eating and not eating. From there, we put the interest in two angles.
Which is it?
We saw that there were regions that control direct ingestion processes that had more vasculature while, on the other hand, there were high-level cognitive areas that had less. The hypothesis is that the structure of the vasculature together with the blood supply have an active and dynamic role in determining both hunger-related and cognitive processes. Therefore, we intend to study the association between obesity and neurodegenerative diseases such as Alzheimer's or cognitive deficit. It is known that in metabolically unhealthy obese humans there is a correlation between their condition and the fact that they are more likely to suffer from Alzheimer's.
In other words, there may be a relationship between obesity and neurodegenerative diseases.
Yes. There are many people who still see obesity as a disease of adipose tissue, when it is a brain pathology: you have anxiety about eating, you eat more, if you don't you're in a bad mood... And it's not only cerebral, it's also chronic, because you've been exposed to a high-fat diet for months or years, so there's been a constant, long-term impact. At the same time, it is a peripheral disease [beyond the brain]: it affects the muscles, the adipose tissue...
Where do you want to start investigating?
We intend to see the most primary processes first. That is, if the fact of eating a diet rich in fat (pastries, hamburgers...) first activates the regions that are controlling hunger, creating more vasculature. And, secondly, if the nutrients that change the vasculature of that region make it more permeable to substances, such as fatty acids, which cross the blood-brain barrier (which is protective) causing inflammation and other less protected regions suffer degeneration processes vascular.
The more vascularity, the more protection?
We believe that the regions that are more vascularized are more protected by being more active. But more cortical regions, more related to cognitive processes, are not so much. And there may be low vascularity due to inflammation, so neurons die and neurodegeneration occurs.
Once you have that neurovasculature, does your body ask you to eat more fatty foods?
It's something we want to explore. We are giving a fat diet to mice in the state, to others that have just been born, to adolescents (between 6 and 8 weeks of age) and to a last group from 12 weeks of life. Thus we will be able to study gestational, early, adolescent and adult obesity and compare how the neurovasculature is. The hypothesis?: We will see more changes in those who started the diet before.
Are these changes reversible?
We want to study it. Once the mouse is obese, we will put it on a diet and exercise. When you have lost weight, we will look at how the vasculature is doing. If we see regions that were altered and remain the same, it means that this exposure at an early age is compromising their functioning as an adult.
I understand that the results from mice can be extrapolated to humans.
The good thing about using the essential metabolic circuits to survive (eating, drinking, regulating body temperature...) is that they are very similar in mice, monkeys and humans. The neurons that regulate hunger in mice are the same as they do in humans. These fundamental aspects for any species have been preserved for centuries, which is why it is beneficial for our body at an evolutionary level to have a fatty diet within its reach.
Because?
Because it still hasn't evolved enough compared to thousands of years ago, when we were in caves and used to going three days without eating because it was necessary to hunt to do so. Now we have any type of food at hand, and for the body to gain weight is something positive, because it has reserves. It is true that there is a moment, when you are obese and the system is so deregulated, that you see it as something negative, but there is no longer time to undo it. When you gain weight, the body fights so you don't lose it.
No exit...
There is currently a new group of drugs, GLP-1 analogues, which have become very popular and are used by some famous actors, who are steadily managing to lose some body weight. But they keep encountering a barrier that they cannot cross. It is impossible for them to go beyond a percentage of weight loss that leads to the return of a normal weight. Because? Because the body lowers metabolic rate, and all this because it sees weight loss as an emergency.
I understand, then, that miracle diets are useless.
None work. You can lose at the beginning, when you may also start to exercise a lot. But the moment you stop that diet, your adipose tissue will recover what it had.
But if you had lost it, why do you recover it?
You had lost it but you are unaware of the molecular genetic defects that have been created in that adipose tissue. For example, the cellular capacity to expend energy may be lower, and by the time you recover the diet you followed before trying to lose weight...
Will there come a time when obesity can be cured with a pill?
I do not think that's possible. However, thanks to research we know more so that we can do more prevention by making sure, for example, that our children follow a good diet and exercise. It is not to alarm anyone, but Spain is the leader in childhood obesity in Europe. If we don't do something, we will also change genetically, our society will be genetically more obese, and then it will be more difficult to act, because we will be born with that predisposition for the nutrients we ingest to convert into fat more easily.
