Guadalupe Sabio, biochemistry: «Obesity is a disease. “We have to stop blaming the patient.”

—One in eight people in the world is obese and more than 40% are overweight. Are we facing the epidemic of the 21st century?

—Yes, due to the fact that obesity and overweight are going to cause many pathologies to increase, especially in old age. In fact, they are already appearing, to the point that we are seeing how life expectancy, which until now had always increased, is being reduced in some countries. It really is an epidemic, but one less noisy than covid.

—Who is to blame: our lifestyle, the food industry?

—I don’t think there is a culprit. Throughout our evolution as a species, we have had to exercise to get food. And we went through periods in which we had a food deficit. Therefore, genetically we are designed to try to transform everything we eat into energy without wasting it. What has happened? That since the industrial revolution we no longer need to move to obtain food, and everything that had genetically benefited us now harms us. We are not made to eat everything we want.

—Are there different types of obesity with different consequences?

-Yeah. And it’s one of the things we’re trying to understand. There are many subtypes of obese people and, in fact, not everyone will develop the same disease. The doctor, when a person with obesity comes to him, knows that he is much more likely to end up with diabetes, cardiovascular disease, a fatty liver or liver cancer, but a priori he does not know which of these pathologies will appear. . One of the interests of our laboratory is to try to stratify the obese population using markers that are in our blood and that are associated with a pathology. Obtain a clear association between cause and consequence, as happens with tobacco and lung cancer.

—Would it mean anticipating the disease and finding new therapeutic targets?

—If we are able to identify each of these biomarkers, we could know which one tells the liver that it is going to develop cancer, which one tells the heart that it has heart failure… But the thing is that also those proteins that are in the blood They also have a function. And if we understand what it is, we could also find new therapeutic targets. For example, a few years ago we saw that men are four times more likely to have liver cancer because their fat is more stressed by testosterone. These signals, the secretion of proteins, could be biomarkers for early diagnosis. It is important, because nowadays liver cancer is detected very late and causes many deaths. If a blood test could detect that someone already has a fibrotic liver and, therefore, the risk of developing cancer in the future, you can try to combat it as soon as possible.

—It is known that there is a clear relationship between obesity and cancer, what is behind it?

—Well, there are several factors. First, obesity produces chronic inflammation, which makes cells more likely to be stimulated and begin to proliferate. But also because obesity itself causes a metabolic change and tumors use it to their advantage. In liver cancer, chronic inflammation affects it, but fat also damages hepatocytes, which begin to die and this sends a signal to the liver that tells it to activate cell proliferation, which increases the probability of producing mutations. random Obesity creates a favorable environment for the tumor to grow and also metastasize. Many investigations try to find out why.

—Does it occur in many types of cancer?

—Yes, there are several cancers that are closely associated with obesity. The liver, the breast, the colon, the ovary…

—Should we consider obesity as a disease in itself? Would they have more financial support for research?

—Yes, but above all because the patients would have a better time. We have to stop blaming them. They are told that they are obese because they eat a lot, because they don’t play sports, because they are lazy… And they carry intrinsic guilt throughout their lives. Let’s see, they hide to eat… With other diseases we are very empathetic, but not with obesity. But the truth is that not all of us have the same basal metabolism. What you eat, absorb and expend is different from person to person, and some have a hard time losing weight. Furthermore, our body has a compensation system, so that once we have gained weight, it does not want to lose it. It is designed so that we reserve everything that he has worked so hard to obtain. It is very difficult for an obese person to get out of this vicious circle. His fat has increased so much that it sends a lot of signals to the brain saying ‘I’m hungry, I’m hungry’. There comes a time when the brain is no longer able to handle it and removes the satiety receptors; no signal tells it to stop eating.

—If the body tends to reserve as much as possible, do intermittent fasting diets make any sense?

—It is still not very clear if intermittent fasting has benefits, but I think it will never work for an obese person. For a diet like this to work for you, you have to control your head very well so that when you eat again, you don’t bloat. Because after a long fast, your body is going to ask you to eat something very energetic. On the other hand, if there are liver problems, diabetes or other pathologies, the stress that fasting for a long time puts on the body is not good either.

—Is Ozempic the miracle that will end obesity?

—It is helping many people with very high levels of obesity. I think it is very important that when you take it you do physical exercise at the same time, because this medication not only reduces fat, but also muscle mass a little. When patients look better and stop pricking themselves, they usually regain the weight they have lost, but in fat, not muscle. In fact, there is now a special interest in trying to understand why this happens and remedy it.

—It seems like it’s a medicine that works for almost everything. They have seen benefits even in psychiatry.

—What happens is that obesity produces a lot of effects that, when eliminated, improve. The first drug that came out against obesity acted on the brain receptors and took away the satisfaction of eating. It had to be withdrawn from the market because it caused depression and there were even people who committed suicide. And for people with obesity, food is the highlight of the day. Ozempic, on the other hand, eliminates anxiety about eating, those horrible desires that often also cause mental problems.

—What consequences will the use of this drug have in the long term?

—It’s still a little premature to reach any conclusion, but I think it will be beneficial. As I said, it must be accompanied by exercise and appropriate eating habits so that when the treatment is removed there is no weight recovery or it is as small as possible. It is similar to what was done until now with stomach bypass. Of course you can take the medication again, but it is not known to what extent it can create resistance in the long term, after many years, and stop having an effect. We will have to see that in the future. The key is to maintain good habits. I always say that a two-month regimen is not ideal, the ideal is to try to give the patient habits and a diet that they can maintain for the rest of their life.

—They have discovered a switch that turns on the desire to play sports. How does it work?

—When we exercise, a protein in our muscles controls the secretion of another, Interleukin-15, which is sent to the brain through the blood and encourages us to exercise more. But there is also another protein that blocks the first, acting as a brake pedal so that the muscle does not suffer. We have seen in mice that the activation of both changes with obesity. When the mice are thin, the one that encourages exercise is much more activated. When they are obese, the brakes prevail. This tells us that obesity affects interest in exercising. Obesity generates mechanisms to try to remain obese. Ultimately it is a defense mechanism, because the more obese you are, the more dangerous it is to exercise too much.

—And how can we press that accelerator more instead of the brake?

—Exercising daily, about 30 or 40 minutes. Interleukin-15 does not have a continuous effect. It has a peak of action and then goes down. In other words, if you exercise once a week, you are not even reaching the stimulation levels for the next time. When we injected this protein into the mice, the effect lasted a maximum of 48 hours, during which time they ran and moved more around their cages. As the mouse has a much faster metabolism, in people it could last three days, I don’t think more. Now we are trying to carry out a project to be able to tell the patient how much the intensity and frequency of his training should be, so that he sees results and is more encouraged.

—Could a pill be made that stimulates the desire to exercise?

—A peptide could be made, a complex injectable molecule. But it is not easy, because it is cutting-edge synthetic chemistry. It would be necessary to look at possible side effects, but not many are anticipated. It is one of the ideas that I most want to do, not only because it would serve to increase voluntary exercise but, in fact, Interleukin-15 also has beneficial effects in the fight against various tumors. Helps the immune system.

—You lead a group of 14 people. Have women begun to occupy positions of influence in science?

—There are many more women at the beginning of their careers, until we are group leaders. But from there, climbing the ladder and being in leadership and decision-making positions is more difficult. You have to see why it happens and the measures to take to avoid it. I think it’s a structural problem. We must admit and be aware that we all, men and women, have biases that, for example, make us choose a man in management positions over a woman, because our brain, which has to make many other decisions, is peace of mind, it’s what you’re used to. That is why there have to be quotas, to try to stop bias.

—If you were Minister of Science, what would be your first decision?

—More investment. Spanish laboratories stretch money in an incredible way. Other countries go in a Ferrari and we go in a Twingo. We can’t compete like this. Additionally, we spend a lot of time asking for money, which prevents us from doing our work. I would also have a structured scientific career that does not depend on whether one political party or another wins. We lose many brilliant scientists along the way because they don’t see a way out. We cannot allow them to not have stability until they are 40 years old. It’s really frustrating.