Noelia Martinez, molecular biologist: “People take medicine when they are sick, but now they think it will help them lose five kilograms” | Health and Wellness

For most of history, humanity’s most pressing problem has been not starving to death, but industrialization has changed the situation for much of the planet. For millions of people, food poses a health risk. The World Health Organization estimates that the number of obese people worldwide has doubled since 1990, to nearly 900 million. Epidemiology shows that poverty is associated with a risk of being overweight, and some researchers have found levels of hormones such as leptin to be the reason why some cannot stop eating even when their body no longer needs the food. But the more research is done, the more it becomes clear that, at least for many overweight people, simple advice like “eat less and move more” is not always helpful.

Noelia Martinez (Santiago de Compostela, 40) works at the University of Oxford (UK) in one of the teams seeking to go further in understanding the underlying mechanisms of obesity. “People have the idea that obesity is the lot of people who sit on the couch, eat a lot and don’t move, that they are lazy. “This lifestyle influences whether you develop obesity or metabolic problems, but there are other factors,” the researcher at the Oxford Center for Diabetes, Endocrinology and Metabolism (OCDEM) explains to EL PAÍS in a video call. “Some cases, some, are associated with genetic mutations. But there are others where an unhealthy lifestyle changes normal metabolic processes and even if we try to reverse it through diet or exercise, the body will not respond,” he adds.

Ask. What can disrupt this balance in the body, leading to obesity?

Reply. You may have a genetic mutation, an underlying curse, that causes this, but there are habits or environmental changes that can upset this balance. In our studies in mice, we see that a diet high in fat or sugar causes changes in various metabolic processes that change, for example, the biological clock that we have inside us. In the article we wrote about in ScienceThe authors expose mice to a high-fat diet, and this disrupts the internal clock of metabolic organs such as the liver. This causes erroneous signals to be sent to the brain, causing the mice to increase their food intake when they should be resting.

I also worked on how the nervous system influences peripheral metabolic organs. If you have a high-fat diet, it will affect the expression of certain genes or the release of neuropeptides in the brain. It is created as a level of toxicity due to high levels of fat, which causes signals to be sent to the periphery and your system begins to accumulate fat where it shouldn’t. For example, in the liver, which is not an organ that should store fat; This is what adipose tissue is needed for.

It has been observed in mice and humans on a high-fat diet that by accumulating so much fat, the adipose tissue begins to produce too much leptin. This hormone sends signals to your brain to stop eating because it tells you that your body fat is fine and you already have enough energy. But a high-fat diet and fat storage disrupt this alert mechanism, and you no longer feel full.

TO. How can they restore balance?

R. Healthy eating and exercise are always key. And then develop a good relationship with food so that if you experience stress or anxiety, you don’t associate it with overeating. The psychological aspect is very important. We are trying to get a good understanding of all these circuits, such as those that connect adipose tissue and the liver or important metabolic organs, as well as the connection to the brain. We think that if we decipher how these pathways function, we may be able to develop a drug that targets them. Imagine, for example, a drug that causes the liver to respond differently to fat, mobilizing it rather than storing it.

Most pharmacological treatments for obesity attempt to activate our sympathetic nervous system to speed up the breakdown of fat. The problem with these treatments is that they not only destroy fat, but also have an effect on the body that can cause tachycardia. Part of my work was to try to genetically determine which nerve fibers went to fat tissue and distinguish them from those that went to the heart. The idea is to develop a drug that activates fat-breaking fibers without activating those that go to the heart, allowing you to lose weight without causing tachycardia.

TO. Is there anything we can do to protect ourselves from the risk of obesity or metabolic problems?

R. Our lifestyle, what we eat, physical activity, if we sleep well – this is the most important thing. If we lead a healthy lifestyle and keep our body as healthy as possible, our body will later have greater metabolic flexibility and be better able to adapt to those external changes that may arise as a result of stress at work or circumstances that change our circadian rhythm.

TO. Can pharmacological solutions play an important role in the fight against obesity?

R. The pharmacological part will be relevant because there comes a time when obese people have such an altered system that no matter how much they exercise or improve their diet, their body will need external help to return to balance. To obtain these very specific drugs, our work accurately describing specific metabolic pathways is essential. This way, we will be able to create drugs with fewer side effects, without allowing a drug that helps burn fat to cause tachycardia or hypertension, for example, as we have seen in mouse models when we activate the sympathetic nervous system. Some mice may even die during treatment because they respond differently to the drug.

So there’s still a long way to go before we can bring these drugs to people so that we can isolate the part of the nervous system that affects the important organs through which it can activate the breakdown of fat. Additionally, it should be taken into account that the vagus nerve, for example, controls the liver, which helps moderate the intake of mice, but it also controls the bladder. Usually people take drugs when they are sick, but now they are considering taking drugs to lose weight and not even when they are obese, but just to lose five kilos. In these cases the approach is completely different because the risk you can take is different.

TO. The importance of circadian rhythms, our internal clock, in maintaining metabolic balance has also been noted.

R. Circadian rhythms are something very complex because it is a system that depends on many signals with a very delicate balance. At the base of our brains there is a central clock that is regulated by light and dark cycles, but our cells and organs have other internal clocks that are partly regulated by central clock signals, but are also regulated. They monitor sleep patterns, daily activities, meal times, rest times, and signals whether you are active or not. People working shifts see these hours changed because when they work at night they are surrounded by darkness, they should be in the inactive phase, but they are in the active phase. Your internal clock is out of sync with what’s happening outside, with the cycle of light and dark. It has been observed that in the long term, it may increase the susceptibility to metabolic problems such as diabetes or fatty liver disease. This is observed primarily in people who constantly change shifts; and less, for example, for those who work all the time at night. In mice, we have used systems that disrupt these light-dark cycles, causing chronic jet lag for several weeks. These mice eventually develop fatty liver disease and numerous inflammatory diseases.

TO. One problem that some people who take GLP-1 agonists, successful anti-obesity drugs, report is that they experience a lack of desire to eat foods that they find unpleasant. Is it possible to remove the desire to eat without taking away other important aspects of pleasure?

R. I don’t work with people, but nutritionists talk about how important it is to remember that we are social animals and that food is much more than just food. It is a social moment of interaction with others as well as a moment of pleasure. Reducing your consumption to a certain level is a positive thing, but you have to be careful that it doesn’t become a problem for you not to be able to sit with your family at Christmas because it won’t help you mentally and you’ll have another Christmas. problem. Moreover, it will not be sustainable.